Elevated O-Linked N-Acetylglucosamine Correlated with Reduced Sp1 Cooperative DNA Binding with Its Collaborating Factors in Vivo

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  • LIM Kihong
    College of Life Sciences and Biotechnology, Korea University
  • CHANG Hyo-Ihl
    College of Life Sciences and Biotechnology, Korea University

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  • Elevated O-Linked<i>N</i>-Acetylglucosamine Correlated with Reduced Sp1 Cooperative DNA Binding with Its Collaborating Factors<i>in Vivo</i>

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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.

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