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Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation
- Source :
- Zeng, J W, Mi, R J, Wang, Y C, Li, Y J, Lin, L, Yao, B, Song, L N, van Die, I, Chapman, A B, Cummings, R D, Jin, P & Ju, T Z 2015, ' Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation ', Journal of Biological Chemistry, vol. 290, no. 31, pp. 19018-19033 . https://doi.org/10.1074/jbc.M115.654244, Journal of Biological Chemistry, 290(31), 19018-19033. American Society for Biochemistry and Molecular Biology Inc.
- Publication Year :
- 2015
-
Abstract
- The T-synthase (core 1 β3-galactosyltransferase) and its molecular chaperone Cosmc regulate the biosynthesis of mucin type O-glycans on glycoproteins, and evidence suggests that both T-synthase and Cosmc are transcriptionally suppressed in several human diseases, although the transcriptional regulation of these two genes is not understood. Here, we characterized the promoters essential for human Cosmc and T-synthase transcription. The upstream regions of the genes lack a conventional TATA box but contain CpG islands, cCpG-I and cCpG-II for Cosmc and tCpG for T-synthase. Using luciferase reporter assays, site-directed mutagenesis, ChIP assays, and mithramycin A treatment, we identified the core promoters within cCpG-II and tCpG, which contain two binding sites for Krüppel-like transcription factors, including SP1/SP3, respectively. Methylome analysis of Tn4 B cells, which harbor a silenced Cosmc, confirmed the hypermethylation of the Cosmc core promoter but not for T-synthase. These results demonstrate that Cosmc and T-synthase are transcriptionally regulated at a basal level by the specificity protein/Krüppel-like transcription factor family of members, which explains their ubiquitous and coordinated expression, and also indicate that they are differentially epigenetically regulated beyond X chromosome imprinting. These results are important in understanding the regulation of these genes that have roles in human diseases, such as IgA nephropathy and cancer.
- Subjects :
- Sp1 Transcription Factor
TATA box
Molecular Sequence Data
Biology
Biochemistry
Gene Expression Regulation, Enzymologic
Epigenesis, Genetic
Sp3 transcription factor
Transcriptional regulation
Humans
Gene Regulation
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Genetics
Regulation of gene expression
Sp1 transcription factor
Binding Sites
Base Sequence
Promoter
Sequence Analysis, DNA
Cell Biology
DNA Methylation
Galactosyltransferases
GC Rich Sequence
HEK293 Cells
Sp3 Transcription Factor
DNA methylation
CpG Islands
Molecular Chaperones
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 290
- Issue :
- 31
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....18caee3b25b10c70b233b0cfdb59bd0e