Abstract
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.
MeSH Terms
Acetylation
Bacterial Proteins
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Basic-Leucine Zipper Transcription Factors
Cyclin D2
Cyclins/genetics
DNA-Binding Proteins/physiology
Gene Expression Regulation
HL-60 Cells
Histones/metabolism
Humans
Promoter Regions, Genetic/physiology
Proto-Oncogene Proteins c-myc/physiology
RNA, Messenger/biosynthesis
RNA-Binding Proteins/physiology
Repressor Proteins
Transcription Factors/physiology
Chemicals
Bacterial Proteins
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Basic-Leucine Zipper Transcription Factors
CCND2 protein, human
Cyclin D2
Cyclins
DNA-Binding Proteins
Histones
MAX protein, human
MXD1 protein, human
MtrB protein, Bacteria
Myc associated factor X
Proto-Oncogene Proteins c-myc
RNA, Messenger
RNA-Binding Proteins
Repressor Proteins
Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bouchard C
Institute for Molecular Biology and Tumor Research, 35033 Marburg, Germany.
Dittrich O
Kiermaier A
Dohmann K
Menkel A
Eilers M
Lüscher B
References (28)
28 references, click to expand
-
Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression.
Cell. 1997 May 2;89(3):349-56
PMID: 9150134
-
Histone deacetylase activity is required for full transcriptional repression by mSin3A.
Cell. 1997 May 2;89(3):341-7
PMID: 9150133
-
Analysis of the DNA-binding activities of Myc/Max/Mad network complexes during induced differentiation of U-937 monoblasts and F9 teratocarcinoma cells.
Oncogene. 1997 Aug 7;15(6):737-48
PMID: 9264414
-
Identification and characterization of specific DNA-binding complexes containing members of the Myc/Max/Mad network of transcriptional regulators.
J Biol Chem. 1998 Mar 20;273(12):6632-42
PMID: 9506959
-
The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.
Cell. 1998 Aug 7;94(3):363-74
PMID: 9708738
-
Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis.
Genes Dev. 1998 Dec 15;12(24):3803-8
PMID: 9869633
-
The ATM-related cofactor Tra1 is a component of the purified SAGA complex.
Mol Cell. 1998 Dec;2(6):863-7
PMID: 9885573
-
c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function.
Nat Genet. 1999 May;22(1):102-5
PMID: 10319872
-
Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27.
EMBO J. 1999 Oct 1;18(19):5321-33
PMID: 10508165
-
The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.
Mol Cell Biol. 2000 Jan;20(2):556-62
PMID: 10611234
-
Gene-target recognition among members of the myc superfamily and implications for oncogenesis.
Nat Genet. 2000 Feb;24(2):113-9
PMID: 10655054
-
Identification of CDK4 as a target of c-MYC.
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2229-34
PMID: 10688915
-
Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion.
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5
PMID: 10737792
-
Mapping DNA target sites of chromatin proteins in vivo by formaldehyde crosslinking.
Methods Mol Biol. 1999;119:455-67
PMID: 10804532
-
Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.
Cell. 2000 Aug 18;102(4):463-73
PMID: 10966108
-
Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression.
Genes Dev. 2000 Sep 1;14(17):2185-91
PMID: 10970882
-
The Myc/Max/Mad network and the transcriptional control of cell behavior.
Annu Rev Cell Dev Biol. 2000;16:653-99
PMID: 11031250
-
Direct examination of histone acetylation on Myc target genes using chromatin immunoprecipitation.
J Biol Chem. 2000 Oct 27;275(43):33798-805
PMID: 10931841
-
Differential activity of conditional MYC and its variant MYC-S in human mortal fibroblasts.
Oncogene. 2000 Oct 26;19(45):5189-97
PMID: 11064456
-
Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression.
Mol Biol Cell. 2000 Nov;11(11):3835-48
PMID: 11071910
-
Identification of c-myc responsive genes using rat cDNA microarray.
Cancer Res. 2000 Nov 1;60(21):5922-8
PMID: 11085504
-
Function of the c-Myc oncoprotein in chromatin remodeling and transcription.
Biochim Biophys Acta. 2001 Mar 21;1471(3):M135-45
PMID: 11250069
-
Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3826-31
PMID: 11274400
-
Dominant negative MYC blocks transformation by ABL oncogenes.
Cell. 1992 Sep 18;70(6):901-10
PMID: 1525828
-
A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation.
Genes Dev. 1993 Nov;7(11):2110-9
PMID: 8224841
-
Mad proteins contain a dominant transcription repression domain.
Mol Cell Biol. 1996 Oct;16(10):5772-81
PMID: 8816491
-
Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression.
Nature. 1997 May 1;387(6628):49-55
PMID: 9139821
-
Cell growth inhibition by the Mad/Max complex through recruitment of histone deacetylase activity.
Curr Biol. 1997 Jun 1;7(6):357-65
PMID: 9197243