E2f6 and Bmi1 cooperate in axial skeletal development

Abstract

Bmi1 is a Polycomb Group protein that functions as a component of Polycomb Repressive Complex 1 (PRC1)to control axial skeleton development through Hox gene repression. Bmi1 also represses transcription of the Ink4a-Arf locus and is consequently required to maintain the proliferative and self-renewal properties of hematopoietic and neural stem cells. Previously, one E2F family member, E2F6, has been shown to interact with Bmi1 and other known PRC1 components. However, the biological relevance of this interaction is unknown. In this study, we use mouse models to investigate the interplay between E2F6 and Bmi1. This analysis shows that E2f6 and Bmi1 cooperate in the regulation of Hox genes, and consequently axial skeleton development, but not in the repression of the Ink4a-Arf locus. These findings underscore the significance of the E2F6 -Bmi1 interaction in vivo and suggest that the Hox and Ink4a-Arf loci are regulated by somewhat different mechanisms.

E2f6-mediated repression of the meioticStag3andSmc1βgenes during early embryonic development requires Ezh2 and not the de novo methyltransferase Dnmt3b

“…7 Even more intriguing is the fact that E2f6 knockout mice, although grossly normal, exhibit mild homeotic transformations of the axial skeleton, a hallmark phenotype for polycomb group protein (PcG) deficiencies. 8,9 Indeed, E2F6 has been shown to interact with RYBP in the context of a BMI1-containing repressive complex, 10 and with EPC1 which itself associates with EZH2. 11 In addition, an E2F6 complex has been described that contains RING1 and HP1γ, which binds to its target promoters in quiescent (G 0 ) cells.…”

Polycomb group complexes – many combinations, many functions

“…Immuno-affinity purification of E2F6 interacting proteins identified Ring1a and Ring1b together with YAF2, H-L(3)MBT-like, DP1, Mga and Max 101. Mutations in mouse E2F6 and Bmi1 have synergistic effects on Hox gene regulation and on axial skeleton development 102. Similarly, Ring1a and Ring1b co-purify with the Bcl6 co-repressor (BCOR) and PCGF1/NSPc1 together with the FBXL10/JHDM1B H3 K36 demethylase and other proteins 103.…”

Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues

“…S7B). In addition, among the genes we have identified as potential Dnmt3b target genes, Slc25a31 and Hoxa11 were already known to be targeted and repressed by E2F6 (38,39). We therefore focused on this particular factor and investigated the interplay between the transcriptional repressor E2F6 and Dnmt3b in the silencing of germ-line genes in somatic tissues.…”