Ring1B Compacts Chromatin Structure and Represses Gene Expression Independent of Histone Ubiquitination

Abstract

SUMMARY How polycomb group proteins repress gene expression in vivo is not known. While histone-modifying activities of the polycomb repressive complexes (PRCs) have been studied extensively, in vitro data have suggested a direct activity of the PRC1 complex in compacting chromatin. Here, we investigate higher-order chromatin compaction of polycomb targets in vivo. We show that PRCs are required to maintain a compact chromatin state at Hox loci in embryonic stem cells (ESCs). There is specific decompaction in the absence of PRC2 or PRC1. This is due to a PRC1-like complex, since decompaction occurs in Ring1B null cells that still have PRC2-mediated H3K27 methylation. Moreover, we show that the ability of Ring1B to restore a compact chromatin state and to repress Hox gene expression is not dependent on its histone ubiquitination activity. We suggest that Ring1B-mediated chromatin compaction acts to directly limit transcription in vivo.

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

“…Indeed, our observations that both L3MBTL2 and L3MBTL1 are expressed throughout pre-implantation development could provide more versatile actions of polycomb-related function at specific genome locations at a given developmental time. While it is known that the catalytic, ubiquitylation activity of PRC1 is not necessary to compact chromatin at the time of gastrulation in vivo 9,17 whether catalytic activity per se of PRC1 is necessary after fertilization, has not been addressed.…”

“…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. 9,12,17 Genetically and biochemically, a role for PRC1 in transcriptional repression has been clearly demonstrated. 33 The initial model for PcG repression posited that PRC1 recruitment depends upon previously established H3K27me3 domains by the action of PRC2.…”

Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation

“…13 Further, transcriptional repression by PRC1 is likely independent of the H2AK119ub mark and rather a function of chromatin condensation. [14][15][16][17] PRC1 is dislocated from chromatin by Zrf1, which tethers to H2AK119ub via a specific ubiquitin-binding domain. 18 Hence, PRC1-mediated ubiquitylation of H2A is a prerequisite for Zrf1 recruitment and thereby PRC1 dislocation.…”

Gene Silencing and Polycomb Group Proteins: An Overview of their Structure, Mechanisms and Phylogenetics

“…Ring1 mediates the ubiquitylation of histone H2A (de Napoles et al, 2004) (for a review, see Martinez and Cavalli, 2006). PRC1 recognizes H3K27me3 to inhibit transcriptional elongation through H2A ubiquitylation (Zhou et al, 2008) and to compact the chromatin structure (Eskeland et al, 2010). PRC2 methylates H3K27 (a key chromatin mark), a main feature of chromatin silencing mediated by PcG proteins.…”

“…PRC2 catalyzes the methylation of H3K27; the methylation of H3K27, particularly trimethylation, is the main hallmark of PcG-mediated silencing (Levine et al, 2004;Ringrose et al, 2003), which occurs through enzymatic activity (in association with PRC1). In addition to the nonenzymatic chromatin-compacting regulatory effect of PRC1 (Eskeland et al, 2010), this Pc complex is able to ubiquitylate histone H2A through Ring1A and Ring1B (for reviews, see Eckert et al, 2011;Richly et al, 2011;Vidal, 2009).…”