title: The CHR site: definition and genome-wide identification of a cell cycle transcriptional element.
abstract: The cell cycle genes homology region (CHR) has been identified as a DNA element with an important role in transcriptional regulation of late cell cycle genes. It has been shown that such genes are controlled by DREAM, MMB and FOXM1-MuvB and that these protein complexes can contact DNA via CHR sites. However, it has not been elucidated which sequence variations of the canonical CHR are functional and how frequent CHR-based regulation is utilized in mammalian genomes. Here, we define the spectrum of functional CHR elements. As the basis for a computational meta-analysis, we identify new CHR sequences and compile phylogenetic motif conservation as well as genome-wide protein-DNA binding and gene expression data. We identify CHR elements in most late cell cycle genes binding DREAM, MMB, or FOXM1-MuvB. In contrast, Myb- and forkhead-binding sites are underrepresented in both early and late cell cycle genes. Our findings support a general mechanism: sequential binding of DREAM, MMB and FOXM1-MuvB complexes to late cell cycle genes requires CHR elements. Taken together, we define the group of CHR-regulated genes in mammalian genomes and provide evidence that the CHR is the central promoter element in transcriptional regulation of late cell cycle genes by DREAM, MMB and FOXM1-MuvB.
authors.affiliation: Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103 Leipzig, Germany gerd.mueller@medizin.uni-leipzig.de.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Müller
authors.affiliation: Computational EvoDevo Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Wintsche
authors.affiliation: Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103 Leipzig, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Stangner
authors.affiliation: Computational EvoDevo Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Prohaska
authors.affiliation: Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, 04103 Leipzig, Germany Center for Non-coding RNA in Technology and Health, Department of Basic Veterinary and Animal Sciences, Faculty of Life Sciences University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C Denmark Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, NM 87501, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103 Leipzig, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Engeland
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics; D005786:Gene Expression Regulation; D018816:Genes, cdc; D016678:Genome; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D014157:Transcription Factors
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