Elevated O-linked N-acetylglucosamine correlated with reduced Sp1 cooperative DNA binding with its collaborating factors in vivo.
O-Linked N-acetylglucosamine (O-GlcNAc), a single GlcNAc modification of proteins, is abundant in nucleocytoplasmic proteins of eukaryotes. Most nuclear transcriptional regulator proteins carry O-GlcNAc, implicating O-GlcNAc in gene regulation. This study suggested the possibility that O-GlcNAc regulates cooperative binding of Sp1 and its collaborating transcription factors, Oct1 and Elf-1, onto DNA templates in vivo. Chromatin immunoprecipitation assays on cells in which O-GlcNAc was modulated pharmacologically revealed that Sp1-Oct1- and Sp1-Elf-1-paired occupancies of previously known target promoter regions were suppressed by elevated O-GlcNAc modification. Since these pairs of transcription factors bind the target promoters cooperatively and DNA binding of Sp1 alone is not affected by O-GlcNAc, our results imply that O-GlcNAc weakens the DNA binding of Sp1 and its cooperative binding partners by inhibiting stable interaction on DNA templates.
Lim
Kihong
K
College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul, Republic of Korea.
Chang
Hyo-Ihl
HI
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012342:RNA, Small Nuclear / Q000235:genetics; D051381:Rats; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D014158:Transcription, Genetic
D012342:RNA, Small Nuclear; D016329:Sp1 Transcription Factor; C405484:U2 small nuclear RNA; D013311:Streptozocin; D004247:DNA; D010100:Oxygen; D000117:Acetylglucosamine