A mechanism of COOH-terminal binding protein-mediated repression.
The E2F4 and E2F5 proteins specifically associate with the Rb-related p130 protein in quiescent cells to repress transcription of various genes encoding proteins important for cell growth. A series of reports has provided evidence that Rb-mediated repression involves both histone deacetylase (HDAC)-dependent and HDAC-independent events. Our previous results suggest that one such mechanism for Rb-mediated repression, independent of recruitment of HDAC, involves the recruitment of the COOH-terminal binding protein (CtBP) corepressor, a protein now recognized to play a widespread role in transcriptional repression. We now find that CtBP can interact with the histone acetyltransferase, cyclic AMP--responsive element--binding protein (CREB) binding protein, and inhibit its ability to acetylate histone. This inhibition is dependent on a NH2-terminal region of CtBP that is also required for transcription repression. These results thus suggest two complementary mechanisms for E2F/p130-mediated repression that have in common the control of histone acetylation at target promoters.
Meloni
Alison R
AR
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3054, Durham, North Carolina 27710, USA.
Lai
Chun-Hsiang
CH
Yao
Tso-Pang
TP
Nevins
Joseph R
JR
D000429:Alcohol Oxidoreductases; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D050882:CREB-Binding Protein; D006655:Histone Deacetylases