Silencing of the meiotic genes SMC1beta and STAG3 in somatic cells by E2F6.
E2F6, a member of the E2F-family of transcription factors, is a retinoblastoma protein-independent transcriptional repressor. E2F6 associates with polycomb group (Pc-G) multiprotein complexes that contain histone H3 methyltransferases, suggesting that E2F6 represses genes by covalent histone modification. However, genes that are repressed by E2F6 via a mechanism that involves histone H3 methylation have not been identified. Using cDNA microarray experiments comparing wild-type and E2f6-/- mouse embryonic fibroblasts, we now found that E2F6 is required to silence the meiosis-specific genes SMC1beta and STAG3 in somatic cells. Re-expression of E2F6 in E2f6-/- cells was sufficient to restore their repression. E2F6 binds in vivo to the promoters of these genes through a conserved binding site. Transcriptional repression of SMC1beta and STAG3 by E2F6 involves multiple mechanisms, including methylation of histone H3 on lysine 9 and lysine 27. Our findings suggest a molecular mechanism for the stable transcriptional silencing of meiotic genes in somatic cells by E2F6.
Storre
Jörg
J
Institute for Molecular Biology and Tumor Research (IMT), Philipps-University Marburg, 35037 Marburg, Germany.
Schäfer
Andrea
A
Reichert
Nina
N
Barbero
José Luis
JL
Hauser
Stefanie
S
Eilers
Martin
M
Gaubatz
Stefan
S
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D050701:E2F6 Transcription Factor / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D017930:Genes, Reporter; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008239:Lysine / Q000737:chemistry; D008540:Meiosis; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D019076:Transgenes; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D050701:E2F6 Transcription Factor; C111236:E2f6 protein, mouse; D006657:Histones; D009687:Nuclear Proteins; D009841:Oligonucleotides; C498637:Stag3 protein, mouse; D000098550:Structural Maintenance of Chromosome Protein 1; D008239:Lysine