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Cosmc Is Silenced in Human Tn4 B Cells through Hypermethylation of the Gene Promoter
Author(s) -
Ju Tongzhong,
Mi Rongjuan,
Song Lina,
Wang Yingchun,
Ding Xiaokun,
Crew Vanja K.,
Lehoux Sylvain D.,
Die Irma,
Chapman Arlene B.,
Cummings Richard D.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.928.7
Subject(s) - microbiology and biotechnology , dna methylation , gene , biology , promoter , bisulfite sequencing , epigenetics , methylation , gene expression , genetics
Background Mucin‐type O‐glycosylation is regulated through core 1 β3‐galatosyltransferase (T‐synthase) and its specific molecular chaperone Cosmc. Human Cosmc is encoded by its gene on Xq24. Genetic alterations of Cosmc , including point mutations and gene deletions, have been identified in several human diseases. Tn4 B cells from patient with Tn‐syndrome‐like features have no transcript of Cosmc and express the Tn antigen (GalNAcα1‐Ser/Thr). Study Objective To elucidate the molecular mechanism as to how human Tn4 B cells lack Cosmc transcripts. Methods Treat Tn4 B cells with 5‐Aza‐2′‐deoxycytidine (5‐Aza‐CdR) to test whether it can induce expression of Cosmc ; and perform bisulfite sequencing to examine the methylation status of the Cosmc promoter. Results Treatment of Tn4 B cells with 5‐Aza‐CdR results in expression of Cosmc transcripts, restores the activity of T‐synthase, and correct the O‐glycosylation. Bisulfite sequencing showed that CG dinucleotides in the Cosmc promoter in Tn4 B cells are exclusively methylated. Interestingly, other X‐linked genes, OGT and PIG‐A are not silenced in the Tn4 B cells. Conclusion Hypermethylation of the Cosmc promoter can completely silence the gene, which is another mechanism that can lead to expression of Tn and STn antigens, which may shed the light on our better understanding of the epigenetic alteration leading to the tumor antigen expression in human tumors.