A Role for E2F6 in the Restriction of Male-Germ-Cell-Specific Gene Expression
| Autor: | Christian Hagemeier, Axel Scholz, Ralf-Jürgen Kuban, Carmen Birchmeier, Michael Pohlers, Bettina Hoffmann, Matthias Truss, Markus Morkel, Michael Strehle, Ute Frede |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Chromatin Immunoprecipitation Molecular Sequence Data DNA Footprinting E2F6 Transcription Factor Electrophoretic Mobility Shift Assay Biology Chromatography Affinity General Biochemistry Genetics and Molecular Biology Mice Tubulin Testis Animals Gene silencing Promoter Regions Genetic E2F Gene DNA Primers Mice Knockout Genetics Regulation of gene expression Binding Sites Base Sequence Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Promoter Sequence Analysis DNA DNA Methylation Microarray Analysis Gene Expression Regulation DNA methylation General Agricultural and Biological Sciences Sequence Alignment E2F Transcription Factors Transcription Factors Binding domain |
| Zdroj: | Current Biology. 15:1051-1057 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2005.04.060 |
| Popis: | E2F transcription factors play a pivotal role in the regulation of cellular proliferation and can be subdivided into activating and repressing family members [1]. Like other E2Fs, E2F6 binds to E2F consensus sites, but in contrast to E2F1-5, it lacks an Rb binding domain and functions as an Rb-independent transcriptional repressor [2, 3, 4 and 5]. Instead, E2F6 has been shown to complex with Polycomb (PcG) group proteins [6 and 7], which have a well-established role in gene silencing. Here, we show that E2F6 plays an unexpected and essential role in the tissue specificity of gene expression. E2F6-deficient mice ubiquitously express the alpha-tubulin 3 and 7 genes, which are expressed strictly testis-specifically in control mice. Like an additional E2F6 target gene, Tex12, that we identified, tubulin 3 and 7 are normally expressed in male germ cells only. The promoters of the alpha-tubulin and Tex12 genes share a perfectly conserved E2F site, which E2F6 binds to. Mechanistically, E2F6-mediated repression involves CpG hypermethylation locking target promoters in an inactive state. Thus, E2F6 is essential for the long-term somatic silencing of certain male-germ-cell-specific genes, but it is dispensable for cell-cycle regulation. |
| Databáze: | OpenAIRE |
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