Myc-mediated transcriptional repression by recruitment of histone deacetylase.
Myc is a transcription factor that features prominently in cancer. The oncogenicity of Myc stems from its ability to regulate expression of genes required for cell growth and proliferation. Although the mechanisms through which Myc activates transcription have been extensively studied, less is known about how Myc represses transcription. Recently, we reported that a conserved element within Myc-MbIII- is important for transcriptional repression. Here, we investigate the mechanism through which MbIII contributes to repression. We show that Myc represses transcription of target genes Id2 and Gadd153 by a process that involves histone deacetylation. We show that MbIII is important for repression of these genes and present evidence that this element contributes to repression by recruiting the histone deacetylase HDAC3 to the Id2 and Gadd153 promoters. These results describe a mechanistic role for MbIII in transcription, and reveal that recruitment of HDAC3 is a process by which Myc represses gene activity.
Kurland
John F
JF
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Tansey
William P
WP
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism*; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D051742:Transcription Factor CHOP / Q000378:metabolism; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D018797:Cell Cycle Proteins; D006655:Histone Deacetylases; D051797:Inhibitor of Differentiation Protein 2; D016271:Proto-Oncogene Proteins c-myc; D051742:Transcription Factor CHOP; D000099186:Histone Deacetylase 3; C497249:DDIT3 protein, human; C497450:ID2 protein, human