title: The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes.
abstract: Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G(0)/G(1). It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G(0). Association of DREAM and cell cycle-dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G(0)/G(1), but also for activation in S, G(2) and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle.
authors: Molecular Oncology, Medical School, University of Leipzig, Semmelweisstrasse 14, 04103 Leipzig, Germany.
authors: Gerd A
authors: GA
authors: Müller
authors: Marianne
authors: M
authors: Quaas
authors: Michael
authors: M
authors: Schümann
authors: Eberhard
authors: E
authors: Krause
authors: Megha
authors: M
authors: Padi
authors: Martin
authors: M
authors: Fischer
authors: Larisa
authors: L
authors: Litovchick
authors: James A
authors: JA
authors: DeCaprio
authors: Kurt
authors: K
authors: Engeland
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D056765:Cyclin B2 / Q000235:genetics*; D005786:Gene Expression Regulation; D018816:Genes, cdc; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics
chemical_list: D056765:Cyclin B2; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes