Lim Kihong, Chang Hyo-Ihl
College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul, Republic of Korea.
Biosci Biotechnol Biochem. 2010;74(8):1668-72. doi: 10.1271/bbb.100289. Epub 2010 Aug 7.
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.
O-连接的N-乙酰葡糖胺（O-GlcNAc）是蛋白质的一种单糖基化修饰，在真核生物的核质蛋白中含量丰富。大多数核转录调节蛋白都带有O-GlcNAc，这表明O-GlcNAc参与基因调控。本研究提示了O-GlcNAc在体内调节Sp1及其协同转录因子Oct1和Elf-1与DNA模板的协同结合的可能性。对经药理学调节O-GlcNAc的细胞进行染色质免疫沉淀分析发现，O-GlcNAc修饰升高会抑制Sp1与Oct1以及Sp1与Elf-1对先前已知靶启动子区域的配对占据。由于这些转录因子对协同结合靶启动子，且单独的Sp1与DNA的结合不受O-GlcNAc影响，我们的结果表明，O-GlcNAc通过抑制在DNA模板上的稳定相互作用来削弱Sp1及其协同结合伙伴与DNA的结合。
