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A role for E2F6 in the restriction of male-germ-cell-specific gene expression

Official URL:https://doi.org/10.1016/j.cub.2005.04.060
PubMed:View item in PubMed
Creators Name:Pohlers, M. and Truss, M. and Frede, U. and Scholz, A. and Strehle, M. and Kuban, R.J. and Hoffmann, B. and Morkel, M. and Birchmeier, C. and Hagemeier, C.
Journal Title:Current Biology
Journal Abbreviation:Curr Biol
Volume:15
Number:11
Page Range:1051-1057
Date:1 January 2005
Keywords:Affinity Chromatography, Base Sequence, Binding Sites, Chromatin Immunoprecipitation, DNA Footprinting, DNA Methylation, DNA Primers, E2F6 Transcription Factor, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Knockout Mice, Microarray Analysis, Molecular Sequence Data, Promoter Regions, Sequence Alignment, Sequence Analysis, DNA, Testis, Transcription Factors, Tubulin, Animals, Mice
Abstract: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 [2-5]. Instead, E2F6 has been shown to complex with Polycomb (PcG) group proteins [6, 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 α-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 α-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.
ISSN:0960-9822
Publisher:Cell Press (U.S.A.)
Item Type:Article

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