Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter.
Myc oncoproteins promote cell cycle progression in part through the transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner. Down-regulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation are critical for transcriptional activation by Myc.
Bouchard
C
C
Institute for Molecular Biology and Tumor Research, 35033 Marburg, Germany.
Dittrich
O
O
Kiermaier
A
A
Dohmann
K
K
Menkel
A
A
Eilers
M
M
Lüscher
B
B
D000107:Acetylation; D001426:Bacterial Proteins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000502:physiology; D012097:Repressor Proteins; D014157:Transcription Factors / Q000502:physiology
D001426:Bacterial Proteins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D004268:DNA-Binding Proteins; D006657:Histones; C499330:MAX protein, human; C079439:MXD1 protein, human; C079092:MtrB protein, Bacteria; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors