Journal articles: 'B4GALNT3'

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Kremer, Jennifer, Cornelia Brendel, Elisabeth Karin Maria Mack, and Hildegard Isolde Dietlinde Mack. "Expression of β-1,4-galactosyltransferases during Aging in Caenorhabditis elegans." Gerontology 66, no. 6 (2020): 571–81. http://dx.doi.org/10.1159/000510722.

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Background: Altered plasma activity of β-1,4-galactosyltransferases (B4GALTs) is a novel candidate biomarker of human aging. B4GALT1 is assumed to be largely responsible for this activity increase, but how it modulates the aging process is unclear at present. Objectives: To determine how expression of B4GALT1 and other B4GALT enzymes changes during aging of an experimentally tractable model organism, Caenorhabditis elegans. Methods: Targeted analysis of mRNA levels of all 3 C. elegans B4GALT family members was performed by qPCR in wild-type and in long-lived daf-2 (insulin/IGF1-like receptor)-deficient or germline-deficient animals. Results: bre-4 (B4GALT1/2/3/4) is the only B4GALT whose expression increases during aging in wild-type worms. In addition, bre-4 levels also rise during aging in long-lived daf-2-deficient worms, but not in animals that are long-lived due to the lack of germline stem cells. On the other hand, expression of sqv-3 (B4GALT7) and of W02B12.11 (B4GALT5/6) appears decreased or constant, respectively, in all backgrounds during aging. Conclusions: The age-dependent bre-4 mRNA increase in C. elegans parallels the age-dependent B4GALT activity increase in humans and is consistent with C. elegans being a suitable experimental organism to define potentially conserved roles of B4GALT1 during aging.

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Mthembu, Yolanda H., Chunsheng Jin, Médea Padra, Jining Liu, Johan Olofsson Edlund, Hanyue Ma, Janos Padra, et al. "Recombinant mucin-type proteins carrying LacdiNAc on different O-glycan core chains fail to support H. pylori binding." Molecular Omics 16, no. 3 (2020): 243–57. http://dx.doi.org/10.1039/c9mo00175a.

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Hsu, Wen-Ming, Mei-Ieng Che, Yung-Feng Liao, Hsiu-Hao Chang, Chia-Hua Chen, Yu-Ming Huang, Yung-Ming Jeng, et al. "B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma." American Journal of Pathology 179, no. 3 (September 2011): 1394–404. http://dx.doi.org/10.1016/j.ajpath.2011.05.025.

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Shauchuk, Auhen, Bożena Szulc, Dorota Maszczak-Seneczko, Wojciech Wiertelak, Edyta Skurska, and Mariusz Olczak. "N-glycosylation of the human β1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization." Glycoconjugate Journal 37, no. 5 (August 22, 2020): 577–88. http://dx.doi.org/10.1007/s10719-020-09941-z.

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Abstract β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis. Herein, we identify two asparagine-linked glycosylation sites in B4GalT4. We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion. Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans. We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.

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Fan, Jingyi, and Huaijun Zhou. "Comprehensive Analysis of GDF10 Methylation Site-Associated Genes as Prognostic Markers for Endometrial Cancer." Journal of Oncology 2022 (October 10, 2022): 1–13. http://dx.doi.org/10.1155/2022/7117083.

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Growth differentiation factor-10 (GDF10) with its methylation trait has recently been found to play a crucial regulatory and communication role in cancers. This investigation aims to identify GDF10 methylation site-associated genes that are closely associated with endometrial cancer (EC) patients’ survival based on normal and UCEC samples from the UCSC Xena database. Our study revealed for the first time that EC exhibited significantly higher levels of GDF10 promoter methylation in comparison with normal tissues. Multiple differentiated methylation sites, which have prognostic value due to their apparent survival differences, were found in the GDF10 promoter region. We performed weighted gene coexpression network analysis (WGCNA) on EC tissues and paraneoplastic tissues while using these differentially methylated sites as phenotypes for selecting the most correlated key modules and their internal genes. To obtain a gene set, the key module genes and differentially expressed genes (DEGs) of EC were intersected. The least absolute shrinkage and selection operator (LASSO) regression along with multivariate Cox regression were performed from the gene set and we screened out the key genes B4GALNT3, DNAJC22, and GREB1. Finally, a prognostic model was validated for effectiveness based on these genes. Additionally, Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC) were applied to assess and verify the model, and they showed good prognosis prediction. Moreover, the differences in risk scores were statistically significant with age, tumor stage, and grade. They may be related to the immune infiltration of tumors as well. In conclusion, based on the methylation-related genes associated with GDF10, we developed a prognosis model for EC patients. It might provide a fresh view for further research and treatment of EC.

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Yi, Hang, Yiwen Lin, Yutong Li, Yeqi Guo, Ligong Yuan, and Yousheng Mao. "Pan-Cancer Analysis of B4GALNT1 as a Potential Prognostic and Immunological Biomarker." Journal of Immunology Research 2022 (July 28, 2022): 1–28. http://dx.doi.org/10.1155/2022/4355890.

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Background. Gangliosides act as important roles in tumor progression. B4GALNT1 is a key enzyme in ganglioside biosynthesis. B4GALNT1 expression is linked to tumorigenesis and the prognosis of tumor patients. Nevertheless, the role of B4GALNT1 in pan-cancer remains unclear. Methods. Several databases, including TCGA, GEO, GTEx, NCI-60, and TIMER, were searched. Methods including correlation analysis, Cox regression analysis, and Kaplan-Meier analysis were used to explore the expression pattern, prognosis, tumor infiltration pattern, genetics and epigenetics, and drug sensitivity of B4GALNT1 in pan-cancer patients from the above datasets. Results. B4GALNT1 was found to be aberrantly expressed in multiple types of tumors. The survival status of tumor patients was significantly related to B4GALNT1 expression, but the correlations were tumor-specific. Moreover, the expression of B4GALNT1 was associated with ImmuneScore and StromalScore in 21 and 27 tumor types, respectively. Also, B4GALNT1 was significantly associated with TMB, MSI, MMR, and DNA methylation. Additionally, the sensitivity of 9 drugs was correlated with the expression of B4GALNT1. Conclusion. A correlation of B4GALNT1 expression with prognosis exists in multiple types of cancers. In addition, B4GALNT1 expression may play a role in TME and tumor immunity regulation. Further investigation of the biological mechanisms of its different roles in tumorigenesis and clinical application as a biomarker is still required.

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Pucci, Michela, Inês Gomes Ferreira, Martina Orlandani, Nadia Malagolini, Manuela Ferracin, and Fabio Dall’Olio. "High Expression of the Sda Synthase B4GALNT2 Associates with Good Prognosis and Attenuates Stemness in Colon Cancer." Cells 9, no. 4 (April 11, 2020): 948. http://dx.doi.org/10.3390/cells9040948.

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Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by B4GALNT2 were studied in LS174T cells transfected with B4GALNT2 cDNA. Results: TCGA data indicate that patients with high B4GALNT2 expression in cancer tissues display longer survival than non-expressers. In LS174T cells, expression of B4GALNT2 did not affect the ability to heal a scratch wound or to form colonies in standard growth conditions but markedly reduced the growth in soft agar, the tridimensional (3D) growth as spheroids, and the number of cancer stem cells, indicating a specific effect of B4GALNT2 on the growth in poor adherence and stemness. On the transcriptome, B4GALNT2 induced the down-regulation of the stemness-associated gene SOX2 and modulated gene expression towards an attenuation of the cancer phenotype. Conclusions: The level of B4GALNT2 can be proposed as a marker to identify higher- and lower-risk colorectal cancer patients.

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Pucci, Michela, Nadia Malagolini, and Fabio Dall’Olio. "Glycosyltransferase B4GALNT2 as a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4331. http://dx.doi.org/10.3390/ijms22094331.

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Background: glycosyltransferase B4GALNT2 and its cognate carbohydrate antigen Sda are highly expressed in normal colon but strongly downregulated in colorectal carcinoma (CRC). We previously showed that CRC patients expressing higher B4GALNT2 mRNA levels displayed longer survival. Forced B4GALNT2 expression reduced the malignancy and stemness of colon cancer cells. Methods: Kaplan–Meier survival curves were determined in “The Cancer Genome Atlas” (TCGA) COAD cohort for several glycosyltransferases, oncogenes, and tumor suppressor genes. Whole expression data of coding genes as well as miRNA and methylation data for B4GALNT2 were downloaded from TCGA. Results: the prognostic potential of B4GALNT2 was the best among the glycosyltransferases tested and better than that of many oncogenes and tumor suppressor genes; high B4GALNT2 expression was associated with a lower malignancy gene expression profile; differential methylation of an intronic B4GALNT2 gene position and miR-204-5p expression play major roles in B4GALNT2 regulation. Conclusions: high B4GALNT2 expression is a strong predictor of good prognosis in CRC as a part of a wider molecular signature that includes ZG16, ITLN1, BEST2, and GUCA2B. Differential DNA methylation and miRNA expression contribute to regulating B4GALNT2 expression during colorectal carcinogenesis.

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Cogez, Virginie, Dorothée Vicogne, Céline Schulz, Lucie Portier, Giulia Venturi, Jérôme de Ruyck, Mathieu Decloquement, et al. "N-Glycan on the Non-Consensus N-X-C Glycosylation Site Impacts Activity, Stability, and Localization of the Sda Synthase B4GALNT2." International Journal of Molecular Sciences 24, no. 4 (February 18, 2023): 4139. http://dx.doi.org/10.3390/ijms24044139.

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The Sda carbohydrate epitope and its biosynthetic B4GALNT2 enzyme are expressed in the healthy colon and down-regulated to variable extents in colon cancer. The human B4GALNT2 gene drives the expression of a long and a short protein isoform (LF-B4GALNT2 and SF-B4GALNT2) sharing identical transmembrane and luminal domains. Both isoforms are trans-Golgi proteins and the LF-B4GALNT2 also localizes to post-Golgi vesicles thanks to its extended cytoplasmic tail. Control mechanisms underpinning Sda and B4GALNT2 expression in the gastrointestinal tract are complex and not fully understood. This study reveals the existence of two unusual N-glycosylation sites in B4GALNT2 luminal domain. The first atypical N-X-C site is evolutionarily conserved and occupied by a complex-type N-glycan. We explored the influence of this N-glycan using site-directed mutagenesis and showed that each mutant had a slightly decreased expression level, impaired stability, and reduced enzyme activity. Furthermore, we observed that the mutant SF-B4GALNT2 was partially mislocalized in the endoplasmic reticulum, whereas the mutant LF-B4GALNT2 was still localized in the Golgi and post-Golgi vesicles. Lastly, we showed that the formation of homodimers was drastically impaired in the two mutated isoforms. An AlphaFold2 model of the LF-B4GALNT2 dimer with an N-glycan on each monomer corroborated these findings and suggested that N-glycosylation of each B4GALNT2 isoform controlled their biological activity.

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Guo, Xiaofei, Xiangyu Wang, Benmeng Liang, Ran Di, Qiuyue Liu, Wenping Hu, Xiaoyun He, Jinlong Zhang, Xiaosheng Zhang, and Mingxing Chu. "Molecular Cloning of the B4GALNT2 Gene and Its Single Nucleotide Polymorphisms Association with Litter Size in Small Tail Han Sheep." Animals 8, no. 10 (September 20, 2018): 160. http://dx.doi.org/10.3390/ani8100160.

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A new fecundity gene named the FecL (mutation), which regulates the ovulation rate, was discovered in French Lacaune sheep. The B4GALNT2 (beta-1, 4-N-acetyl-galactosaminyl transferase 2) gene was considered as the potential FecL mutation gene. This study explores whether the effect of the FecL mutation exists in other sheep breeds, and the features of the B4GALNT2 gene in terms of the molecular structure and its expression profile. Using Sanger sequencing, we found that high and low fecundity breeds from among 11 measured sheep breeds all had no variation in the three specific mutation sites, which were linked with the FecL mutation. However, two mutations of g.36946470C > T and g.36933082C > T in the exon of B4GALNT2 had a significant effect on litter size in the first parity for Small Tail Han (STH) Sheep (p < 0.05). Two transcription start sites (TSS) of B4GALNT2 in its 5′-flanking region were discovered in ovine granule cells in vitro, through the RACE (Rapid amplification of cDNA ends) method. Except for in the kidney and oviduct, no significant difference in expression levels had been found between STH sheep and Tan sheep breeds. The B4GALNT2 gene, as a candidate for FecL, may have a relationship with the differences in litter size in STH sheep. B4GALNT2 is mainly expressed in the ovine ovary, which also suggests that B4GALNT2 plays an important role in sheep reproduction.

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Pucci, Michela, Inês Gomes Ferreira, Nadia Malagolini, Manuela Ferracin, and Fabio Dall’Olio. "The Sda Synthase B4GALNT2 Reduces Malignancy and Stemness in Colon Cancer Cell Lines Independently of Sialyl Lewis X Inhibition." International Journal of Molecular Sciences 21, no. 18 (September 8, 2020): 6558. http://dx.doi.org/10.3390/ijms21186558.

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Background: The Sda antigen and its biosynthetic enzyme B4GALNT2 are highly expressed in healthy colon but undergo a variable down-regulation in colon cancer. The biosynthesis of the malignancy-associated sialyl Lewis x (sLex) antigen in normal and cancerous colon is mediated by fucosyltransferase 6 (FUT6) and is mutually exclusive from that of Sda. It is thought that the reduced malignancy associated with high B4GALNT2 was due to sLex inhibition. Methods: We transfected the cell lines SW480 and SW620, derived respectively from a primary tumor and a metastasis of the same patient, with the cDNAs of FUT6 or B4GALNT2, generating cell variants expressing either the sLex or the Sda antigens. Transfectants were analyzed for growth in poor adherence, wound healing, stemness and gene expression profile. Results: B4GALNT2/Sda expression down-regulated all malignancy-associated phenotypes in SW620 but only those associated with stemness in SW480. FUT6/sLex enhanced some malignancy-associated phenotypes in SW620, but had little effect in SW480. The impact on the transcriptome was stronger for FUT6 than for B4GALNT2 and only partially overlapping between SW480 and SW620. Conclusions: B4GALNT2/Sda inhibits the stemness-associated malignant phenotype, independently of sLex inhibition. The impact of glycosyltransferases on the phenotype and the transcriptome is highly cell-line specific.

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Dall’Olio, Fabio, Michela Pucci, and Nadia Malagolini. "The Cancer-Associated Antigens Sialyl Lewisa/x and Sda: Two Opposite Faces of Terminal Glycosylation." Cancers 13, no. 21 (October 21, 2021): 5273. http://dx.doi.org/10.3390/cancers13215273.

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Terminal carbohydrate structures are particularly relevant in oncology because they can serve as cancer markers and alter the phenotype of cancer cells. The Sda antigen and the sialyl Lewisx and sialyl Lewisa (sLex and sLea) antigens are terminal structures whose biosynthesis is mutually exclusive. In this review, we describe the main features of the Sda antigen in cancer and its relationship with sLex/a antigens. Information was obtained from an extensive literature search and from The Cancer Genome Atlas (TCGA) public database. The Sda biosynthetic enzyme B4GALNT2 undergoes downregulation in colorectal (CRC) and stomach cancer, while it is ectopically expressed by a minority of breast cancer (BRCA) patients. High expression of B4GALNT2 is associated with better prognosis and a less malignant gene expression profile in CRC, while the opposite occurs in BRCA. The regulation of B4GALNT2 expression in CRC is multifactorial, involving gene methylation and miRNA expression. Forced expression of B4GALNT2 inhibited sLea/sLex and reduced malignancy and stemness in cells constitutively expressing sLex/a antigens. However, consistent effects were observed upon B4GALNT2 forced expression and in cells not expressing sLex/a antigens. Thus, B4GALNT2 and the Sda antigen exert a tumor-restraining activity in CRC and probably other gastrointestinal cancers, independently of sLex/a antigens.

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Yesmin, Farhana, Robiul H. Bhuiyan, Yuhsuke Ohmi, Yuki Ohkawa, Orie Tajima, Tetsuya Okajima, Keiko Furukawa, and Koichi Furukawa. "Aminoglycosides are efficient reagents to induce readthrough of premature termination codon in mutant B4GALNT1 genes found in families of hereditary spastic paraplegia." Journal of Biochemistry 168, no. 2 (May 27, 2020): 103–12. http://dx.doi.org/10.1093/jb/mvaa041.

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Abstract The readthrough of premature termination codon (PTC) by ribosome sometimes produces full-length proteins. We previously reported a readthrough of PTC of glycosyltransferase gene B4GALNT1 with hereditary spastic paraplegia (HSP). Here we featured the readthrough of B4GALNT1 of two mutants, M4 and M2 with PTC by immunoblotting and flow cytometry after transfection of B4GALNT1 cDNAs into cells. Immunoblotting showed a faint band of full-length mutant protein of M4 but not M2 at a similar position with that of wild-type B4GALNT1. AGC sequences at immediately before and after the PTC in M4 were critical for the readthrough. Treatment of cells transfected with mutant M4 cDNA with aminoglycosides resulted in increased readthrough of PTC. Furthermore, treatment of transfectants of mutant M2 cDNA with G418 also resulted in the induction of readthrough of PTC. Both M4 and M2 cDNA transfectants showed increased/induced bands in immunoblotting and GM2 expression in a dose-dependent manner of aminoglycosides. Results of mass spectrometry supported this effect. Here, we showed for the first time the induction and/or enhancement of the readthrough of PTCs of B4GALNT1 by aminoglycoside treatment, suggesting that aminoglycosides are efficient for patients with HSP caused by PTC of B4GALNT1, in which gradual neurological disorders emerged with aging.

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Pucci, Michela, Martina Duca, Nadia Malagolini, and Fabio Dall’Olio. "Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models." Cancers 14, no. 9 (April 24, 2022): 2128. http://dx.doi.org/10.3390/cancers14092128.

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Background: Glycosylation changes are a main feature of cancer. Some carbohydrate epitopes and expression levels of glycosyltransferases have been used or proposed as prognostic markers, while many experimental works have investigated the role of glycosyltransferases in malignancy. Using the transcriptomic data of the 21 TCGA cohorts, we correlated the expression level of 114 glycosyltransferases with the overall survival of patients. Methods: Using the Oncolnc website, we determined the Kaplan–Meier survival curves for the patients falling in the 15% upper or lower percentile of mRNA expression of each glycosyltransferase. Results: Seventeen glycosyltransferases involved in initial steps of N- or O-glycosylation and of glycolipid biosynthesis, in chain extension and sialylation were unequivocally associated with bad prognosis in a majority of cohorts. Four glycosyltransferases were associated with good prognosis. Other glycosyltransferases displayed an extremely high predictive value in only one or a few cohorts. The top were GALNT3, ALG6 and B3GNT7, which displayed a p < 1 × 10−9 in the low-grade glioma (LGG) cohort. Comparison with published experimental data points to ALG3, GALNT2, B4GALNT1, POFUT1, B4GALT5, B3GNT5 and ST3GAL2 as the most consistently malignancy-associated enzymes. Conclusions: We identified several cancer-associated glycosyltransferases as potential prognostic markers and therapeutic targets.

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Pucci, Michela, Martina Duca, Nadia Malagolini, and Fabio Dall’Olio. "Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models." Cancers 14, no. 9 (April 24, 2022): 2128. http://dx.doi.org/10.3390/cancers14092128.

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Background: Glycosylation changes are a main feature of cancer. Some carbohydrate epitopes and expression levels of glycosyltransferases have been used or proposed as prognostic markers, while many experimental works have investigated the role of glycosyltransferases in malignancy. Using the transcriptomic data of the 21 TCGA cohorts, we correlated the expression level of 114 glycosyltransferases with the overall survival of patients. Methods: Using the Oncolnc website, we determined the Kaplan–Meier survival curves for the patients falling in the 15% upper or lower percentile of mRNA expression of each glycosyltransferase. Results: Seventeen glycosyltransferases involved in initial steps of N- or O-glycosylation and of glycolipid biosynthesis, in chain extension and sialylation were unequivocally associated with bad prognosis in a majority of cohorts. Four glycosyltransferases were associated with good prognosis. Other glycosyltransferases displayed an extremely high predictive value in only one or a few cohorts. The top were GALNT3, ALG6 and B3GNT7, which displayed a p < 1 × 10−9 in the low-grade glioma (LGG) cohort. Comparison with published experimental data points to ALG3, GALNT2, B4GALNT1, POFUT1, B4GALT5, B3GNT5 and ST3GAL2 as the most consistently malignancy-associated enzymes. Conclusions: We identified several cancer-associated glycosyltransferases as potential prognostic markers and therapeutic targets.

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Tanihara, Fuminori, Maki Hirata, Nhien Thi Nguyen, Osamu Sawamoto, Takeshi Kikuchi, and Takeshige Otoi. "One-Step Generation of Multiple Gene-Edited Pigs by Electroporation of the CRISPR/Cas9 System into Zygotes to Reduce Xenoantigen Biosynthesis." International Journal of Molecular Sciences 22, no. 5 (February 24, 2021): 2249. http://dx.doi.org/10.3390/ijms22052249.

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Xenoantigens cause hyperacute rejection and limit the success of interspecific xenografts. Therefore, genes involved in xenoantigen biosynthesis, such as GGTA1, CMAH, and B4GALNT2, are key targets to improve the outcomes of xenotransplantation. In this study, we introduced a CRISPR/Cas9 system simultaneously targeting GGTA1, CMAH, and B4GALNT2 into in vitro-fertilized zygotes using electroporation for the one-step generation of multiple gene-edited pigs without xenoantigens. First, we optimized the combination of guide RNAs (gRNAs) targeting GGTA1 and CMAH with respect to gene editing efficiency in zygotes, and transferred electroporated embryos with the optimized gRNAs and Cas9 into recipient gilts. Next, we optimized the Cas9 protein concentration with respect to the gene editing efficiency when GGTA1, CMAH, and B4GALNT2 were targeted simultaneously, and generated gene-edited pigs using the optimized conditions. We achieved the one-step generation of GGTA1/CMAH double-edited pigs and GGTA1/CMAH/B4GALNT2 triple-edited pigs. Immunohistological analyses demonstrated the downregulation of xenoantigens; however, these multiple gene-edited pigs were genetic mosaics that failed to knock out some xenoantigens. Although mosaicism should be resolved, the electroporation technique could become a primary method for the one-step generation of multiple gene modifications in pigs aimed at improving pig-to-human xenotransplantation.

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Johnsen, Jill, John Baines, Diethard Tautz, and David Ginsburg. "The B4galnt2 Regulatory Polymorphism, Mvwf1, Causes Low VWF Levels and Segregates in Natural Mouse Populations." Blood 108, no. 11 (November 16, 2006): 542. http://dx.doi.org/10.1182/blood.v108.11.542.542.

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Abstract We previously identified the cause of low levels of von Willebrand factor (VWF) in the RIIIS/J mouse strain to be a regulatory mutation, Mvwf1, in an N-acetylgalactosaminyltransferase, B4galnt2 (previously designated Galgt2). Mvwf1 causes a tissue-specific switch in B4galnt2 expression from intestinal epithelium to vascular endothelium, resulting in aberrant glycosylation of VWF and accelerated clearance from circulation. We have identified thirteen Mvwf1 inbred mouse strains that share this remarkable tissue-specific switch and a common 97kb haplotype block, including a 30kb region of 2–3% sequence divergence that flanks Exon 1. An RIIIS/J BAC transgene containing the entire Mvwf1 haplotype block and B4galnt2 gene confers vascular gene expression, while C57BL6/J BAC transgenes spanning the homologous region confer “wild-type” vessel(−), intestine(+) gene expression, indicating that one or more tissue-specific regulatory elements sufficient to recapitulate the Mvwf1 tissue-specific switch lie within the genomic region covered by these BACs. A wild-derived recombinant Mvwf1 allele containing the 3′ half of the Mvwf1 haplotype block confers the vessel(−), intestine(+) B4galnt2 expression pattern, placing the regulatory mutation(s) responsible for the Mvwf1 switch well upstream of the proximal promoter region. Sequence analysis of DNA from wild-caught individual mice confirmed the presence of a highly conserved wild mouse Mvwf1 founder allele that likely pre-dates the development of the inbred mouse strains. PCR of genomic DNA from wild caught mice representing M. m. musculus, M. m. domesticus, M. m. castaneus, M. m. molossinus, M. spretus, M. hortulanis, and M. macedonicus revealed that the Mvwf1 allele is common in wild M. m. domesticus populations in North America, Europe, and Africa, with an allele frequency as high as 60% in French mice. Population samples of M. m. domesticus from Cologne, Germany and the Massif Central region of France drastically differ in the frequency of this allele (0% vs. 60%). A significant reduction in microsatellite variability at B4galnt2 in the French population, as measured by the lnRH statistic, suggests a recent, local shift in the frequency of Mvwf1, likely due to a recent change in selective pressure. Analysis of independently trapped wild mice from the Massif Central region of France confirmed that Mvwf1 confers vascular endothelial B4galnt2 expression and causes significantly lower VWF levels (5.5+2.0 vs. 13.3+2.3, p<1x10−7) in this population. These data support a B4Galnt2 allele-specific survival advantage in wild mice, leading us to speculate that a similar survival advantage could account for the high prevalence of VWD in human populations.

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Stenfelt, Linn, Jonas Nilsson, Åsa Hellberg, Yew Wah Liew, Jenny Morrison, Göran Larson, and Martin L. Olsson. "Glycoproteomic and Phenotypic Elucidation of B4GALNT2 Expression Variants in the SID Histo-Blood Group System." International Journal of Molecular Sciences 23, no. 7 (April 1, 2022): 3936. http://dx.doi.org/10.3390/ijms23073936.

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The Sda histo-blood group antigen (GalNAcβ1-4(NeuAcα2-3)Galβ-R) is implicated in various infections and constitutes a potential biomarker for colon cancer. Sd(a−) individuals (2–4% of Europeans) may produce anti-Sda, which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sd(a++)/Cad phenotype are involved. We previously reported the association of B4GALNT2 mutations with Sd(a−), which established the SID blood-group system. The present study provides causal proof underpinning this correlation. Sd(a−) HEK293 cells were transfected with different B4GALNT2 constructs and evaluated by immunostaining and glycoproteomics. The predominant SIDnull candidate allele with rs7224888:T>C (p.Cys406Arg) abolished Sda synthesis, while this antigen was detectable as N- or O-glycans on glycoproteins following transfection of wildtype B4GALNT2. Surprisingly, two rare missense variants, rs148441237:A>G and rs61743617:C>T, found in a Sd(a−) compound heterozygote, gave results similar to wildtype. To elucidate on whether Sd(a++)/Cad also depends on B4GALNT2 alterations, this gene was sequenced in five individuals. No Cad-specific changes were identified, but a detailed erythroid Cad glycoprotein profile was obtained, especially for glycophorin-A (GLPA) O-glycosylation, equilibrative nucleoside transporter 1 (S29A1) O-glycosylation, and band 3 anion transport protein (B3AT) N-glycosylation. In conclusion, the p.Cys406Arg β4GalNAc-T2 variant causes Sda-deficiency in humans, while the enigmatic Cad phenotype remains unresolved, albeit further characterized.

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Wang, Pu, Xiaolong Li, and Yuan Xie. "B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382098010. http://dx.doi.org/10.1177/1533033820980104.

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Our study was designed to investigate the role of B4GalT1 in glioblastoma, in vitro and in vivo, to detect whether B4GalT1 knockdown could regulate the development of glioblastoma, and further observe the relationship between B4GalT1 knockdown and the apoptosis and autophagy of glioblastoma. To begin, we looked at TCGA and GEPIA systems to predict the potential function of B4GalT1. Western blot and RT-PCR were used to analyze the expression, or mRNA level, of B4GalT1 at different tissue or cell lines. Next, the occurrence and development of glioblastoma, in vitro and in vivo, was observed by using B4GalT1 knocked down by lentivirus. Finally, the apoptosis and autophagy of glioblastoma was observed in vitro and in vivo. Results show that B4GalT1 was a highly variable gene, and GEPIA and TCGA systems show B4GalT1 expression in GBM tumor tissue was higher than in normal tissue. Pair-wise gene correlation analysis revealed a probable relationship between B4GalT1 and autophagy related proteins. The B4GalT1 expression and mRNA level were increased in tumor cells, or U87 cells. B4GalT1 knocked down by lentivirus could inhibit glioblastoma development, in vitro and in vivo, by reducing tumor weight and volume, increasing survival, and weakening tumor cells proliferation, migration, invasion. B4GalT1 knockdown could increase apoptosis and autophagy of glioblastoma in vitro and in vivo. Our study demonstrates that B4GalT1 may be able to regulate apoptosis and autophagy of glioblastoma. Bax, Bcl-2, cleaved caspase-3, Beclin-1, and LC3 s may be the downstream target factors of B4GalT1 in apoptosis and autophagy, which may provide a new strategy to reduce glioblastoma development by regulating apoptosis and autophagy.

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Picardo, Francesco, Antonella Romanelli, Laura Muinelo-Romay, Tommaso Mazza, Caterina Fusilli, Paola Parrella, Jorge Barbazán, et al. "Diagnostic and Prognostic Value of B4GALT1 Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer." Cancers 11, no. 10 (October 19, 2019): 1598. http://dx.doi.org/10.3390/cancers11101598.

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Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan–Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592–0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC.

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De Vitis, Claudia, Michela D’Ascanio, Andrea Sacconi, Dario Pizzirusso, Valentina Salvati, Massimiliano Mancini, Giorgia Scafetta, et al. "B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis." International Journal of Molecular Sciences 23, no. 23 (November 30, 2022): 15040. http://dx.doi.org/10.3390/ijms232315040.

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Idiopathic pulmonary fibrosis (IPF) is a disease characterized by progressive scarring of the lung that involves the pulmonary interstitium. The disease may rapidly progress, leading to respiratory failure, and the long-term survival is poor. There are no accurate biomarkers available so far. Our aim was to evaluate the expression of the B4GALT1 in patients with IPF. Analysis of B4GALT1 gene expression was performed in silico on two gene sets, retrieved from the Gene Expression Omnibus database. Expression of B4GALT1 was then evaluated, both at the mRNA and protein levels, on lung specimens obtained from lung biopsies of 4 IPF patients, on one IPF-derived human primary cell and on 11 cases of IPF associated with cancer. In silico re-analysis demonstrated that the B4GALT1 gene was overexpressed in patients and human cell cultures with IPF (p = 0.03). Network analysis demonstrated that B4GALT1 upregulation was correlated with genes belonging to the EMT pathway (p = 0.01). The overexpression of B4GALT1 was observed, both at mRNA and protein levels, in lung biopsies of our four IPF patients and in the IPF-derived human primary cell, in other fibrotic non-lung tissues, and in IPF associated with cancer. In conclusion, our results indicate that B4GALT1 is overexpressed in IPF and could represent a novel marker of this disease.

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Yoon, Seungwon, Seulgi Lee, Chungyu Park, Hyunyong Choi, Minwoo Yoo, Sang Chul Lee, Cheol-Ho Hyun, et al. "An Efficacious Transgenic Strategy for Triple Knockout of Xeno-Reactive Antigen Genes GGTA1, CMAH, and B4GALNT2 from Jeju Native Pigs." Vaccines 10, no. 9 (September 8, 2022): 1503. http://dx.doi.org/10.3390/vaccines10091503.

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Pigs are promising donors of biological materials for xenotransplantation; however, cell surface carbohydrate antigens, including galactose-alpha-1,3-galactose (α-Gal), N-glycolylneuraminic acid (Neu5Gc), and Sd blood group antigens, play a significant role in porcine xenograft rejection. Inactivating swine endogenous genes, including GGTA1, CMAH, and B4GALNT2, decreases the binding ratio of human IgG/IgM in peripheral blood mononuclear cells and erythrocytes and impedes the effectiveness of α-Gal, Neu5Gc, and Sd, thereby successfully preventing hyperacute rejection. Therefore, in this study, an effective transgenic system was developed to target GGTA1, CMAH, and B4GALNT2 using CRISPR-CAS9 and develop triple-knockout pigs. The findings revealed that all three antigens (α-Gal, Neu5Gc, and Sd) were not expressed in the heart, lungs, or liver of the triple-knockout Jeju Native Pigs (JNPs), and poor expression of α-Gal and Neu5G was confirmed in the kidneys. Compared with the kidney, heart, and lung tissues from wild-type JNPs, those from GGTA1/CMAH/ B4GALNT2 knockout-recipient JNPs exhibited reduced human IgM and IgG binding and expression of each immunological rejection component. Hence, reducing the expression of swine xenogeneic antigens identifiable by human immunoglobulins can lessen the immunological rejection against xenotransplantation. The findings support the possibility of employing knockout JNP organs for xenogeneic transplantation to minimize or completely eradicate rejection using multiple gene-editing methods.

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Sha, Jichen, Rongrong Zhang, Jiteng Fan, Yong Gu, Yiqing Pan, Jing Han, Xiaoyan Xu, Shifang Ren, and Jianxin Gu. "The B-Cell-Specific Ablation of B4GALT1 Reduces Cancer Formation and Reverses the Changes in Serum IgG Glycans during the Induction of Mouse Hepatocellular Carcinoma." Cancers 14, no. 5 (March 4, 2022): 1333. http://dx.doi.org/10.3390/cancers14051333.

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Serum immunoglobulin G (IgG) glycosylation, especially galactosylation, has been found to be related to a variety of tumors, including hepatocellular carcinoma (HCC). However, whether IgG glycan changes occur in the early stages of HCC formation remains unclear. We found that the galactosylation level increased and that the related individual glycans showed regular changes over the course of HCC induction. Then, the effect of the B-cell-specific ablation of β1,4galactosyltransferase 1 (CKO B4GALT1) and B4GALT1 defects on the IgG glycans that were modified during the model induction process and HCC formation is investigated in this study. CKO B4GALT1 reduces serum IgG galactosylation levels and reduces cancer formation. Furthermore, insignificant changes in the B-cell B4GALT1 and unchanged serum IgG galactosylation levels were found during cancer induction in female mice, which might contribute to the lower cancer incidence in female mice than in male mice. The gender differences observed during glycan and B4GALT1 modification also add more evidence that the B4GALT1 in B cells and in serum IgG galactosylation may play an important role in HCC. Therefore, the findings of the present research can be used to determine the methods for the early detection of HCC as well as for prevention.

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Byrne, Guerard, Saadullah Ahmad-Villiers, Zeji Du, and Christopher McGregor. "B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen." Xenotransplantation 25, no. 5 (March 31, 2018): e12394. http://dx.doi.org/10.1111/xen.12394.

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Byrne, G. W., Z. Du, H. Kogelberg, and C. McGregor. "Porcine B4GALNT2 a Source of New Xenogenic Glycan." Journal of Heart and Lung Transplantation 34, no. 4 (April 2015): S150—S151. http://dx.doi.org/10.1016/j.healun.2015.01.405.

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Wavelet-Vermuse, Cindy, Sophie Groux-Degroote, Dorothée Vicogne, Virginie Cogez, Giulia Venturi, Marco Trinchera, Guillaume Brysbaert, et al. "Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1." Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1864, no. 11-12 (November 2021): 194747. http://dx.doi.org/10.1016/j.bbagrm.2021.194747.

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Perota, A., I. Lagutina, C. Quadalti, R. Duchi, P. Turini, G. Crotti, S. Colleoni, et al. "203 SINGLE-STEP GENE EDITING OF 3 XENOANTIGENS IN PORCINE FIBROBLASTS USING PROGRAMMABLE NUCLEASES." Reproduction, Fertility and Development 29, no. 1 (2017): 210. http://dx.doi.org/10.1071/rdv29n1ab203.

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Programmable nucleases (ZFN, Tal Effector Nucleases, and CRISPR) opened a new era for mammal genome editing, in particular for the pigs used for xenotransplantation. Multiple gene editing events are required both for knockout (KO) of xenoantigens and for targeted integration of human protective genes (Perota et al. 2016 J. Genet. Genomics 43, 233–23). The objective of the present work was to edit selected pig lines to KO the enzymes coding for the most relevant xenoantigens (i.e. GGTA1, CMAH, and B4GalNT2), combining Talens and CRISPR/Cas9 technologies to magnetic beads selection (Li et al. 2013 Xenotransplantation 22, 20–31). Primary porcine adult fibroblasts were transfected using Nucleofector (V-024 program). In a single reaction 2 × 106 fibroblasts were co-transfected using 2 different sets of TALENS (4 μg/set) specific for CMAH (Conchon et al., 2013) and GGTA1 (Perota et al., 2015) genes together with B4GalNT2-specific CRISPR/Cas9 expression vector (2 μg; pX330-B4GalNT2; Estrada et al., 2015). Eight days post-transfection (DPT), Gal–/– cells were selected initially using biotin-conjugated IB4 lectin (Sigma, St. Louis, MO, USA) and magnetic beads (Dynabeads M-280, Thermo Fisher Scientific, Waltham, MA, USA). The selected cells were then plated on 150-mm Petri dishes (200 cells/dish) and cultured for 10 days. Selected colonies were expanded for PCR analysis and cryopreserved for somatic cell nuclear transfer (SCNT). All colonies were analysed by PCR for CMAH gene and their resulting products were digested with HindIII (HindIII-RFLP). Colonies that lost wild-type HindIII as a consequence of Talens effected deletion were PCR characterised for GGTA1, selecting those that had detectable Indels after gel electrophoresis and finally analysed by PCR for B4GalNT2. All PCR products were validated by sequencing for all the 3 genes of interest (TopoTA, Thermo Fisher Scientific). Selected colonies were used as nuclear donors for SCNT (Lagutina et al., 2006). Eight DPT we obtained 3.45 ×106 cells. About 6.0 × 103 Gal-negative cells (0.17%) were collected from the supernatant after magnetic beads separation. Eighteen DPT, 120 colonies were picked up and their HindIII-RFLP analyses on CMAH gene revealed that 22 colonies (18.3%) were KO for both CMAH alleles. Of these 22 colonies following electrophoretic analyses of GGTA1-PCR products, 13 colonies had detectable Indels. These 13 colonies were finally PCR analysed and sequenced for B4GalNT2 and sequenced. Final sequencing results confirmed that 2 colonies (1.6%) resulted in KO for the 3 genes. Three different zona-free SCNT experiments were done and 579 reconstructed embryos were obtained. On Day 7, 322 morulae or blastocysts (56%) were transferred in 3 synchronised sows and 2 (66%) became pregnant. In conclusion, after gene editing with programmable nucleases, combining beads-mediated selection with well-designed molecular analyses, we developed a multistep assay that can be used efficiently to detect desired gene edited events in cell colonies suitable for the SCNT. Embryos generated after SCNT were able to establish pregnancies at a high rate. This work is supported by European FP7 grants Translink (n° 603049) and Xenoislet (n° 601827).

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Wu, Tao, Yifei Li, and Baodong Chen. "B4GALT3 promotes cell proliferation and invasion in glioblastoma." Neurological Research 42, no. 6 (March 21, 2020): 463–70. http://dx.doi.org/10.1080/01616412.2020.1740465.

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Boraska, Vesna, Vesela Torlak, Veselin Škrabić, Zrinka Kačić, Jasminka Jakšić, Gordana Stipančić, Anita Špehar Uroić, Anita Markotić, and Tatijana Zemunik. "Glycosyltransferase B4GALNT1 and type 1 diabetes in Croatian population." Clinical Biochemistry 42, no. 9 (June 2009): 819–22. http://dx.doi.org/10.1016/j.clinbiochem.2009.01.012.

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SADAN, TINA, JAMUNA VALSALAN, THIRUPATHY VENKETACHALAPATHY, and T. V. ARAVINDAKSHAN. "Prl and B4GALT-1 gene polymorphism and their association with milk production traits in crossbred cattle of Kerala." Indian Journal of Animal Sciences 90, no. 10 (April 5, 2021): 1383–86. http://dx.doi.org/10.56093/ijans.v90i10.111315.

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The main objective of present study was to explore the genetic variation in exon 3 of PRL (185 bp) and exon-2 of B4GALT-1 (256 bp) locus and analyze their associations with milk production traits. The study was conducted on 200 crossbred cattle distributed in different farms under Kerala Veterinary and Animal Sciences University and field centres of ICAR-FPT scheme, Mannuthy. Polymorphism of both the genes was detected by Single Strand Confirmation Polymorphism (PCR-SSCP). Similar banding pattern were noticed in exon-3 region of PRL, population was found to be monomorphic, indicating conserved nature of this fragment in the screened crossbred cattle population of Kerala. Two unique band patterns were detected in 256 bp fragment of B4GALT-1. Sequencing revealed a nonsynonymous single nucleotide variation in c.521T>C in exon 2 of B4GALT-1, resulted in an amino acid substitution of methionine to threonine due to a codon change of ATG to ACG. Different genetic variants of B4GALT-1 was significantly associated with 305 days milk yield and protein percent. The study indicates the existence of genetic variability in B4GALT-1 gene on crossbred cattle population of Kerala and suggests a scope of considering genetic variants of B4GALT-1 gene in selection of cattle for higher milk production.

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Li, Pei-Tzu, Chi-Jr Liao, Lung-Chi Yu, Wen-Guey Wu, and Sin Tak Chu. "Localization of B4GALNT2 and its role in mouse embryo attachment." Fertility and Sterility 97, no. 5 (May 2012): 1206–12. http://dx.doi.org/10.1016/j.fertnstert.2012.02.019.

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Rivadeneyra, Leonardo, Melissa M. Lee-Sundlov, Simon Glabere, Heather Ashwood, Robert Burns, and Karin M. Hoffmeister. "Sialylated Glycans Regulate MUC13 and the Proto-Oncogenes Pim-1 and Myc to Control Hematopoietic Stem and Progenitor Cell Numbers." Blood 136, Supplement 1 (November 5, 2020): 8. http://dx.doi.org/10.1182/blood-2020-143365.

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The enzyme β-1-4 galactosyltransferase 1 (β4GalT1) plays a critical role in thrombopoiesis by modulating sialo-glycan (sialyl N-acetyl-lactosamine or LacNAc) content and function of the β1 integrin on megakaryocytes (MKs) (Nat. Commun. 2020;11(1):356). Recent data, however, point to a more complex role for β4GalT1 in hematopoiesis, as the promoter region of its conserved gene, B4galt1, is rich in enhancer sequences for transcription factors associated with cell identity and pro-oncogenic regulatory programs. Here, we investigated the homeostasis of hematopoietic stem and progenitor cells (HSPCs) in B4galt1-/- mice. We demonstrate that lack of Sialylated LacNAc synthesis perturbs HSPCs beyond the homing deficiency associated with lack of homing sialo-glycan motifs. Flow cytometry analysis showed that B4galt1-/- mouse bone marrows have increased numbers of Long-Term HSCs (LT-HSCs, defined as LineageNeg/Sca-1Pos/c-KitPos/CD150Pos/CD48Neg). The increase in HSC numbers led us to investigate their phenotypic and functional features further. While quiescence markers in B4galt1-/- LT-HSCs were indistinguishable relative to controls, LT-HSCs expressed more of the platelet marker CD41 on their surface, supporting a highly expanded CD41+ subset of LT-HSCs. Platelet-bias of LT-HSCs has been associated with inflammation and aging. However, our data do not support an increased cytokine inflammatory profile in the bone marrow. Instead, single-cell RNA sequencing (scRNA seq) of sorted β4galt1-/- LineageNeg/Sca-1Pos/c-KitPos (LSK) cells showed a significantly increased expression of the proto-oncogene Pim-1, its target, Myc, and the heavily O-glycosylated transmembrane receptor mucin 13 (MUC13), compared to control cells. Analysis of LT-HSC glycan expression using lectin microarray showed the expected decrease in N-glycosylation associated with B4galt1 deficiency, but also an increase in O-glycans, consistent with overexpression of MUC13, expression of which was enriched compared to other surface mucins. The data show that B4galt1 deletion leads to overexpression of the proto-oncogenes Pim-1, Myc, and MUC13 in HSPCs. The data suggest that MUC13-associated O-glycans and glyco-synthetic genes are potential therapeutic targets for hematologic malignancies since mucins have anti-inflammatory functions and alterations in mucin expression are with inflammation and cancer. Disclosures No relevant conflicts of interest to declare.

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De Vitis, Claudia, Giacomo Corleone, Valentina Salvati, Francesca Ascenzi, Matteo Pallocca, Francesca De Nicola, Maurizio Fanciulli, et al. "B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells." Journal of Clinical Medicine 8, no. 11 (November 9, 2019): 1928. http://dx.doi.org/10.3390/jcm8111928.

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Background: According to the cancer stem cells (CSCs) hypothesis, a population of cancer cells with stem cell properties is responsible for tumor propagation, drug resistance, and disease recurrence. Study of the mechanisms responsible for lung CSCs propagation is expected to provide better understanding of cancer biology and new opportunities for therapy. Methods: The Lung Adenocarcinoma (LUAD) NCI-H460 cell line was grown either as 2D or as 3D cultures. Transcriptomic and genome-wide chromatin accessibility studies of 2D vs. 3D cultures were carried out using RNA-sequencing and Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), respectively. Reverse transcription polymerase chain reaction (RT-PCR) was also carried out on RNA extracted from primary cultures derived from malignant pleural effusions to validate RNA-seq results. Results: RNA-seq and ATAC-seq data disentangled transcriptional and genome accessibility variability of 3D vs. 2D cultures in NCI-H460 cells. The examination of genomic landscape of genes upregulated in 3D vs. 2D cultures led to the identification of 2D cultures led to the identification of Beta-1,4-galactosyltranferase 1 (B4GALT1) as the top candidate. B4GALT1 as the top candidate. B4GALT1 was validated as a stemness factor, since its silencing caused strong inhibition of 3D spheroid formation. Conclusion: Combined transcriptomic and chromatin accessibility study of 3D vs. 2D LUAD cultures led to the identification of B4GALT1 as a new factor involved in the propagation and maintenance of LUAD CSCs.

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Baba, Hayato, Mitsuro Kanda, Yusuke Sato, Koichi Sawaki, Dai Shimizu, Masahiko Koike, Satoru Motoyama, Yasuhiro Kodera, and Tsutomu Fujii. "Expression and Malignant Potential of B4GALNT4 in Esophageal Squamous Cell Carcinoma." Annals of Surgical Oncology 27, no. 9 (April 6, 2020): 3247–56. http://dx.doi.org/10.1245/s10434-020-08431-8.

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Melin, Kyle, Jorge Duconge, and Dagmar F. Hernandez Suarez. "2220." Journal of Clinical and Translational Science 1, S1 (September 2017): 25. http://dx.doi.org/10.1017/cts.2017.99.

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OBJECTIVES/SPECIFIC AIMS: The objective of this study is to measure the association of CYP2C19 (*1-*8,*17), ABCB1(C3435T; rs1045642), PON1 (p.Q192R; rs662), and B4GALT2 (c.909 C>T and c.366 G>C) gene polymorphisms in the Caribbean Hispanic population with major adverse cardiovascular events (MACE). METHODS/STUDY POPULATION: Patients of Caribbean Hispanic ethnicity from all geographic regions of the Island of Puerto Rico, male and female, aged >21 will be recruited. Cases will consist of patients receiving a daily clopidogrel dose of 75 mg following acute coronary syndrome (ACS) who experience a MACE within the first year of treatment. Control study patients must have received clopidogrel 75 mg daily for a minimum of 1 year without experiencing MACE. Genomic DNA samples will be genotyped to determine the frequency distribution of major CYP2C19, ABCB1, PON1, and B4GALT2 gene polymorphisms. Observed frequencies will be compared with other reported populations. An association study will be performed between genetic variables and MACE and a multivariable logistic regression model (additive) will be constructed. RESULTS/ANTICIPATED RESULTS: We anticipate finding a significant association between major genetic determinants of clopidogrel response and MACE where cases with MACE will carry higher frequency of CYP2C19, ABCB1, PON1, and B4GALT2. DISCUSSION/SIGNIFICANCE OF IMPACT: As the range of multiloci allelic combinations in admixed Caribbean Hispanics is higher than in other populations due to its unique 500-year history of genomic admixture, a wide spectrum of genetic variances is expected to be present in the study population. Determining the prevalence and effect of CYP2C19, ABCB1, PON1, and B4GALT2 polymorphisms holds the potential to personalize anti-platelet treatment for Caribbean Hispanic patients requiring treatment after ACS.

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Harlalka, Gaurav V., Anna Lehman, Barry Chioza, Emma L. Baple, Reza Maroofian, Harold Cross, Ajith Sreekantan-Nair, et al. "Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis." Brain 136, no. 12 (October 6, 2013): 3618–24. http://dx.doi.org/10.1093/brain/awt270.

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Rose, Laura, Katherine Hall, Sha Tang, Linda Hasadsri, and Virginia Kimonis. "Homozygous B4GALNT1 mutation and biochemical glutaric acidemia type II: A case report." Clinical Neurology and Neurosurgery 189 (February 2020): 105553. http://dx.doi.org/10.1016/j.clineuro.2019.105553.

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Li, Pei-Tzu, Chi-Jr Liao, Wen-Guey Wu, Lung-Chi Yu, and Sin Tak Chu. "Progesterone-regulated B4galnt2 expression is a requirement for embryo implantation in mice." Fertility and Sterility 95, no. 7 (June 2011): 2404–9. http://dx.doi.org/10.1016/j.fertnstert.2011.03.043.

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Mayo, Lior, Sunia Trauger, Manon Blain, Ivan Mascanfroni, Pia Kivisäkk, Ada Yeste, Rohit Bakshi, et al. "B4GALT6 regulates astrocyte activation during CNS inflammation (INM8P.360)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 195.4. http://dx.doi.org/10.4049/jimmunol.194.supp.195.4.

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Abstract Astrocytes play complex roles in neuroinflammation. Thus, it is important to characterize the mechanisms regulating astrocyte function, as well as potential targets for the therapeutic modulation of astrocyte activity. Here we report that during the chronic-progressive phase of EAE, astrocytes promote disease pathogenesis by a lipid-dependent signaling pathway. In line with previous studies, depletion of reactive astrocytes during the acute phase of chronic-progressive EAE exacerbated disease. However, depletion of astrocytes in the chronic phase ameliorated the disease. Hence, to understand this dichotomy we compared gene expression profiles of astrocytes from mice in acute and chronic stages of EAE. One gene associated with the chronic stage was B4GALT6, which codes for the β-1,4-galactosyltransferase 6 that catalyzes the synthesis of lactosylceramide (LacCer). We observed that LacCer levels are upregulated in the CNS during chronic EAE, and that LacCer synthesized by the astrocytes acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of infiltrating monocytes and microglia, and neurodegeneration. We also detected increased B4GALT6 expression and LacCer levels in MS lesions. Finally, the inhibition of LacCer synthesis suppressed CNS innate immunity and neurodegeneration, and interfered with the activation of human astrocytes. Thus, B4GALT6 is a potential therapeutic target for MS and neuroinflammatory disorders.

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Bhuiyan, Robiul H., Yuhsuke Ohmi, Yuki Ohkawa, Pu Zhang, Maiko Takano, Noboru Hashimoto, Tetsuya Okajima, Keiko Furukawa, and Koichi Furukawa. "Loss of Enzyme Activity in Mutated B4GALNT1 Gene Products in Patients with Hereditary Spastic Paraplegia Results in Relatively Mild Neurological Disorders: Similarity with Phenotypes of B4galnt1 Knockout Mice." Neuroscience 397 (January 2019): 94–106. http://dx.doi.org/10.1016/j.neuroscience.2018.11.034.

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Rausch, Philipp, Natalie Steck, Abdulhadi Suwandi, Janice A. Seidel, Sven Künzel, Kirandeep Bhullar, Marijana Basic, et al. "Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection." PLOS Pathogens 11, no. 7 (July 2, 2015): e1005008. http://dx.doi.org/10.1371/journal.ppat.1005008.

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Caraffi, Maini, Ivanovski, Pollazzon, Giangiobbe, Valli, Rossi, et al. "Severe Peripheral Joint Laxity is a Distinctive Clinical Feature of Spondylodysplastic-Ehlers-Danlos Syndrome (EDS)-B4GALT7 and Spondylodysplastic-EDS-B3GALT6." Genes 10, no. 10 (October 12, 2019): 799. http://dx.doi.org/10.3390/genes10100799.

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Variations in genes encoding for the enzymes responsible for synthesizing the linker region of proteoglycans may result in recessive conditions known as “linkeropathies”. The two phenotypes related to mutations in genes B4GALT7 and B3GALT6 (encoding for galactosyltransferase I and II respectively) are similar, characterized by short stature, hypotonia, joint hypermobility, skeletal features and a suggestive face with prominent forehead, thin soft tissue and prominent eyes. The most outstanding feature of these disorders is the combination of severe connective tissue involvement, often manifesting in newborns and infants, and skeletal dysplasia that becomes apparent during childhood. Here, we intend to more accurately define some of the clinical features of B4GALT7 and B3GALT6-related conditions and underline the extreme hypermobility of distal joints and the soft, doughy skin on the hands and feet as features that may be useful as the first clues for a correct diagnosis.

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Baba, Hayato, Mitsuro Kanda, Yasuhiro Kodera, and Tsutomu Fujii. "ASO Author Reflections: Expression and Malignant Potential of B4GALNT4 in Esophageal Squamous Cell Carcinoma." Annals of Surgical Oncology 27, no. 9 (April 10, 2020): 3257–58. http://dx.doi.org/10.1245/s10434-020-08458-x.

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Staubach, Fabian, Sven Künzel, Andrea C. Baines, Andrew Yee, Beth M. McGee, Fredrik Bäckhed, John F. Baines, and Jill M. Johnsen. "Expression of the blood-group-related glycosyltransferase B4galnt2 influences the intestinal microbiota in mice." ISME Journal 6, no. 7 (January 26, 2012): 1345–55. http://dx.doi.org/10.1038/ismej.2011.204.

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Dall'Olio, Fabio, Nadia Malagolini, Mariella Chiricolo, Marco Trinchera, and Anne Harduin-Lepers. "The expanding roles of the Sda/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2." Biochimica et Biophysica Acta (BBA) - General Subjects 1840, no. 1 (January 2014): 443–53. http://dx.doi.org/10.1016/j.bbagen.2013.09.036.

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Harrus, Deborah, Fawzi Khoder-Agha, Miika Peltoniemi, Antti Hassinen, Lloyd Ruddock, Sakari Kellokumpu, and Tuomo Glumoff. "The dimeric structure of wild-type human glycosyltransferase B4GalT1." PLOS ONE 13, no. 10 (October 23, 2018): e0205571. http://dx.doi.org/10.1371/journal.pone.0205571.

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Dad, Rubina, Uzma Malik, Aneela Javed, Berge A. Minassian, and Muhammad Jawad Hassan. "Structural annotation of Beta-1,4- N -acetyl galactosaminyltransferase 1 (B4GALNT1) causing Hereditary Spastic Paraplegia 26." Gene 626 (August 2017): 258–63. http://dx.doi.org/10.1016/j.gene.2017.05.041.

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Galeev, Alibek, Abdulhadi Suwandi, Aleksa Cepic, Meghna Basu, John F. Baines, and Guntram A. Grassl. "The role of the blood group-related glycosyltransferases FUT2 and B4GALNT2 in susceptibility to infectious disease." International Journal of Medical Microbiology 311, no. 3 (April 2021): 151487. http://dx.doi.org/10.1016/j.ijmm.2021.151487.

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Wu, Jie, Lun Xiao, Haixia Zhou, Hong Liu, Yue Ge, Jing Yang, Yuanyuan Li, Depei Wu, Yun Zhao, and Xiuyan Zhang. "ZFX modulates the growth of human leukemic cells via B4GALT1." Acta Biochimica et Biophysica Sinica 48, no. 12 (October 26, 2016): 1120–27. http://dx.doi.org/10.1093/abbs/gmw109.

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Wu, Jie, Lun Xiao, Haixia Zhou, Hong Liu, Yue Ge, Jing Yang, Yuanyuan Li, Depei Wu, Yun Zhao, and Xiuyan Zhang. "ZFX modulates the growth of human leukemic cells via B4GALT1." Acta Biochimica et Biophysica Sinica 50, no. 5 (March 9, 2018): 522. http://dx.doi.org/10.1093/abbs/gmy012.

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Journal articles on the topic 'B4GALNT3'

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