PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos

Abstract

In eukaryotes, Suv39h H3K9 trimethyltransferases are required for pericentric heterochromatin formation and function. In early mouse preimplantation embryos, however, paternal pericentric heterochromatin lacks Suv39h-mediated H3K9me3 and downstream marks. Here we demonstrate Ezh2-independent targeting of maternally provided polycomb repressive complex 1 (PRC1) components to paternal heterochromatin. In Suv39h2 maternally deficient zygotes, PRC1 also associates with maternal heterochromatin lacking H3K9me3, thereby revealing hierarchy between repressive pathways. In Rnf2 maternally deficient zygotes, the PRC1 complex is disrupted, and levels of pericentric major satellite transcripts are increased at the paternal but not the maternal genome. We conclude that in early embryos, Suv39h-mediated H3K9me3 constitutes the dominant maternal transgenerational signal for pericentric heterochromatin formation. In absence of this signal, PRC1 functions as the default repressive back-up mechanism. Parental epigenetic asymmetry, also observed along cleavage chromosomes, is resolved by the end of the 8-cell stage--concurrent with blastomere polarization--marking the end of the maternal-to-embryonic transition.

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

“…In early embryos, heterochromatic sequences are differentially marked in pronuclei of maternal and paternal origins [61]. Maternal heterochromatin carries Suv39h2-dependent H3K9 trimethylation, which is inherited from the oocyte and is required for maintenance of the canonical heterochromatic state in embryos.…”

“…In paternal heterochromatin, which lacks this mark, proteins of the Polycomb Repressive Complex 1 (a major repressive complex implicated in epigenetic repression of e.g. developmental regulatory genes during development [62]) mediate transcriptional repression of heterochromatin associated satellites sequences [61]. In addition to roles for histone methylation associated with repressive chromatin, trimethylation of H3K4, an active mark, has also been shown to be important in the female germline.…”

Characterization of non-canonical Polycomb Repressive Complex 1 subunits during early mouse embryogenesis

“…4,14 Among them, H3K27me3, catalyzed by the Polycomb Repressive Complex 2 (PRC2) and, in general, Polycomb group (PcG) proteins have been shown to play important roles from the earliest stages of development. 8,25,27 At large, PcG repression is achieved through 2 major types of complexes that mediate various biochemical functions including histone modifying activities, recognition of covalent modifications, and physical compaction of chromatin. PRC2 displays its main catalytic activity toward H3K27me3 while the main catalytic activity of PRC1 is monoubiquitylation of H2A at lysine 119 (K119), although PRC1 has also been shown to be able to compact chromatin independently of H2AK119ub in vitro and in vivo.…”

L’hétérochromatine constitutive dans tous ses états

“…Dans les zygotes, les génomes parentaux sont épigénétiquement asymé-triques [15,41] (➜). Dans ces cellules, l'hétérochromatine est organisée en anneaux autour des précurseurs des nucléoles [16,17] ; alors que l'hétérochromatine maternelle est associée avec les marques épigénétiques conventionnelles (H3K9me2/3 et HP1β), la plupart de ces marques sont absentes au niveau de l'hétérochromatine paternelle (pour revue, voir [3]). Étonnamment, elles y sont remplacées par d'autres modifications épigénétiques dont H3K27me3, et la présence du complexe de répres-sion PRC1 (Polycomb repressive complex 1) [17].…”

“…Dans ces cellules, l'hétérochromatine est organisée en anneaux autour des précurseurs des nucléoles [16,17] ; alors que l'hétérochromatine maternelle est associée avec les marques épigénétiques conventionnelles (H3K9me2/3 et HP1β), la plupart de ces marques sont absentes au niveau de l'hétérochromatine paternelle (pour revue, voir [3]). Étonnamment, elles y sont remplacées par d'autres modifications épigénétiques dont H3K27me3, et la présence du complexe de répres-sion PRC1 (Polycomb repressive complex 1) [17]. Par ailleurs, dans les cellules souches embryonnaires défi-cientes pour les HMT Suv39h1/h2, la marque H3K27me3, établie par la protéine PcG Ezh2 et caractéristique de l'hétérochromatine facultative, est aussi enrichie au niveau de l'hétérochromatine constitutive [18].…”