Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.
The Hairy-related bHLH proteins function as transcriptional repressors in most cases and play important roles in diverse aspects of metazoan development. Recently, it was shown that the Drosophila bHLH repressor proteins, Hairy and Deadpan, bind to and function with the NAD(+)-dependent histone deacetylase, Sir2. Here we demonstrate that the human Sir2 homologue, SIRT1, also physically associates with the human bHLH repressor proteins, hHES1 and hHEY2, both in vitro and in vivo. Moreover, using the reporter assay, we show that both SIRT1-dependent and -independent deacetylase pathways are involved in the transcriptional repressions mediated by these bHLH repressors. These results indicate that the molecular association between bHLH proteins and Sir2-related proteins is conserved among metazoans, from Drosophila to human, and suggest that the Sir2-bHLH interaction also plays important roles in human cells.
Takata
Takehiko
T
Laboratory of Molecular and Cellular Assembly, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Ishikawa
Fuyuki
F
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056564:Sirtuin 1; D037761:Sirtuins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C078493:HES1 protein, human; C447939:SIRT1 protein, human