Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development

Abstract

Polycomb-repressive complex 2 (PRC2) catalyzes the methylation of histone H3 Lys27 (H3K27) and functions as a critical epigenetic regulator of both stem cell pluripotency and somatic differentiation, but its role in male germ cell development is unknown. Using conditional mutagenesis to remove the core PRC2 subunits EED and SUZ12 during male germ cell development, we identified a requirement for PRC2 in both mitotic and meiotic germ cells. We observed a paucity of mutant spermatogonial stem cells (SSCs), which appears independent of repression of the known cell cycle inhibitors Ink4a/Ink4b/Arf. Moreover, mutant spermatocytes exhibited ectopic expression of somatic lamins and an abnormal distribution of SUN1 proteins on the nuclear envelope. These defects were coincident with abnormal chromosome dynamics, affecting homologous chromosome pairing and synapsis. We observed acquisition of H3K27me3 on stage-specific genes during meiotic progression, indicating a requirement for PRC2 in regulating the meiotic transcriptional program. Together, these data demonstrate that transcriptional repression of soma-specific genes by PRC2 facilitates homeostasis and differentiation during mammalian spermatogenesis.

Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development

“…Ezh1/2 2KO mice were previously reported (Ezhkova et al , 2011). Eed floxed and Suz12 floxed mice were generously provided by Weipeng Mu and Terry Magnuson (Mu et al , 2014). As previously described with Ezh1/2 2KO mice, mice null for EED or Suz12 die shortly after birth, and all analysis of these mice after P0 was performed on grafted skin obtained using the previously described full-thickness grafting protocol (Ezhkova et al , 2011).…”

“…We would like to thank Weipeng Mu and Terry Magnuson for their generous gift of the Suz12 floxed and EED floxed mice (Mu et al , 2014). The Ezh1 mutant mice were generated at the Research Institute of Molecular Pathology (IMP, Vienna) by Donal O'Carroll (laboratory of Thomas Jenuwein) with the help of Maria Sibilia (laboratory of Erwin Wagner).…”

Murine and Human Spermatids Are Characterized by Numerous, Newly Synthesized and Differentially Expressed Transcription Factors and Bromodomain-Containing Proteins

“…A highly conserved silencing mechanism is mediated by the Polycomb repressive complexes PRC1 and PRC2 [19]. In the male germline, these complexes play essential roles in mitotic and meiotic phases [20][21][22]. Transcriptional silencing in haploid spermatids could be caused by the histone-to-protamine transition that occurs during spermiogenesis in elongating spermatids after the bulk of transcription [23].…”

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

“…Many PcG null mutations of one of the orthologs in mice can survive to later embryonic stages; some of them are even viable, showing very mild phenotypes [94] (see Tables 2-5). Furthermore, analyzing the mouse phenotypes of late lethal PcG mutations, it became obvious that although these factors play profound role in homeotic regulation [158,159], their epigenetic repressor functions are also important in hematopoiesis [160][161][162][163] (reviewed in [164] and [165]), neuronal [154,166] (reviewed in [167]) cardiac [168][169][170] and skeletal muscle differentiation [171], as well as in the maintenance of germ cell fate [172][173][174][175].…”