p300 provides a corepressor function by cooperating with YY1 and HDAC3 to repress c-Myc.
We showed earlier that p300/CBP plays an important role in G1 progression by negatively regulating c-Myc and thereby preventing premature G1 exit. Here, we have studied the mechanism by which p300 represses c-Myc and show that in quiescent cells p300 cooperates with histone deacetylase 3 (HDAC3) to repress transcription. p300 and HDAC3 are recruited to the upstream YY1-binding site of the c-Myc promoter resulting in chromatin deacetylation and repression of c-Myc transcription. Consistent with this, ablation of p300, YY1 or HDAC3 expression results in chromatin acetylation and induction of c-Myc. These three proteins exist as a complex in vivo and form a multiprotein complex with the YY1-binding site in vitro. The C-terminal region of p300 is both necessary and sufficient for the repression of c-Myc. These and other results suggest that in quiescent cells the C-terminal region of p300 provides corepressor function and facilitates the recruitment of p300 and HDAC3 to the YY1-binding site and represses the c-Myc promoter. This corepressor function of p300 prevents the inappropriate induction of c-Myc and S phase.
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
N
N
Sankar
S
S
Baluchamy
R-K
RK
Kadeppagari
G
G
Singhal
S
S
Weitzman
B
B
Thimmapaya
D000107:Acetylation; D001665:Binding Sites; D050882:CREB-Binding Protein / Q000502:physiology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000502:physiology*; D016259:Genes, myc; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism; D024363:Transcription Initiation Site; D050986:YY1 Transcription Factor / Q000502:physiology*; D000099186:Histone Deacetylase 3
D050882:CREB-Binding Protein; D002843:Chromatin; D050881:E1A-Associated p300 Protein; D006655:Histone Deacetylases; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D050986:YY1 Transcription Factor; D000099186:Histone Deacetylase 3; C489427:MYC protein, human; C494698:YY1 protein, human; C494363:CREBBP protein, human; C494360:EP300 protein, human