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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-150704 |
| Date | 18 August 2014 |
| Creators | Müller, Gerd A., Wintsche, Axel, Stangner, Konstanze, Prohaska, Sonja J., Stadler, Peter F., Engeland, Kurt |
| Contributors | Universität Leipzig, Medizinische Fakultät, Universität Leipzig, Fakultät für Mathematik und Informatik, Max-Planck-Institut für Mathematik in den Naturwissenschaften,, University of Copenhagen, Faculty of Life Sciences, Santa Fe Institute,, Oxford Journals, |
| Publisher | Universitätsbibliothek Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:article |
| Format | application/pdf |
| Source | Nucleic Acids Research, 2014 doi:10.1093/nar/gku696 |
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