Abstract
Silencing of the Meiotic Genes SMC1β and STAG3 in Somatic Cells by E2F6
Highlights
E2F proteins are transcription factors that regulate genes with key roles in cell cycle progression, synthesis of nucleotides, DNA replication, DNA repair, and apoptosis
In this study we focused on two genes that were strongly up-regulated in E2F6-deficient cells and that encode for STAG3 and SMC1, meiotic specific subunits of the cohesin complex (19 –21)
We used immunoblotting with a STAG3-specific polyclonal antiserum and with lysates from E2f6Ϫ/Ϫ mouse embryonic fibroblasts (MEFs) to test whether STAG3 is increased on the protein level (Fig. 1C)
Summary
E2F proteins are transcription factors that regulate genes with key roles in cell cycle progression, synthesis of nucleotides, DNA replication, DNA repair, and apoptosis (for a review, see Ref. 1). E2F1, E2F2, and E2F3a are potent transcriptional activators Their major role is to activate genes that are involved in proliferation and apoptosis. E2F3b, E2F4, and E2F5 function primarily as active transcriptional repressors through binding to the retinoblastoma tumor suppressor protein and related pocket proteins. A mechanism for transcriptional repression by E2F6 was suggested by the observation that E2F6 associates with polycomb proteins and histone methyltransferases [11,12,13]. No evidence for a role of histone H3 methylation in repression of these genes was found on these promoters. We report a novel function of E2F6 to stably repress certain meiotic genes in somatic cells through multiple mechanisms including methylation of histone H3 on lysine 9 and lysine 27
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