Silencing of the Meiotic Genes SMC1� and STAG3 in Somatic Cells by E2F6 (original) (raw)

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 SMC1␤ 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 SMC1␤ 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.

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