Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression.
Transcription factors and RNA polymerase II can be modified by O-linked N-acetylglucosamine (O-GlcNAc) monosaccharides at serine or threonine residues, yet the precise functional roles of this modification are largely unknown. Here, we show that O-GlcNAc transferase (OGT), the enzyme that catalyzes this posttranslational modification, interacts with a histone deacetylase complex by binding to the corepressor mSin3A. Functionally, OGT and mSin3A cooperatively repress transcription in parallel with histone deacetylation. We propose that mSin3A targets OGT to promoters to inactivate transcription factors and RNA polymerase II by O-GlcNAc modification, which acts in concert with histone deacetylation to promote gene silencing in an efficient and specific manner.
Yang
Xiaoyong
X
Department of Medicine, Division of Endocrinology and Metabolism, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zhang
Fengxue
F
Kudlow
Jeffrey E
JE
D000828:Animal Population Groups; D000818:Animals; D019556:COS Cells; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D006023:Glycoproteins; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex