Stabilization of Chromatin Structure by PRC1, a Polycomb Complex

Abstract

The Polycomb group (PcG) genes are required for maintenance of homeotic gene repression during development. Mutations in these genes can be suppressed by mutations in genes of the SWI/SNF family. We have purified a complex, termed PRC1 (Polycomb repressive complex 1), that contains the products of the PcG genes Polycomb, Posterior sex combs, polyhomeotic, Sex combs on midleg, and several other proteins. Preincubation of PRC1 with nucleosomal arrays blocked the ability of these arrays to be remodeled by SWI/SNF. Addition of PRC1 to arrays at the same time as SWI/SNF did not block remodeling. Thus, PRC1 and SWI/SNF might compete with each other for the nucleosomal template. Several different types of repressive complexes, including deacetylases, interact with histone tails. In contrast, PRC1 was active on nucleosomal arrays formed with tailless histones.

Epigenetic regulations in hematopoietic Hox code

“…Thus, the PRC1 complex is hypothesized to create a stably repressed chromatin structure through recognition of the E(z)-mediated H3K27 trimethylation. In addition, PRC1 inhibits chromatin remodeling by SWI-SNF chromatin-remodeling complexes (Shao et al, 1999;Saurin et al, 2001;Francis et al, 2004) and maintains a repressive chromatin structure. The presence of TATA-binding protein Associated Factors in PRC1 suggests that its components might prevent the transition from recruitment to the promoter to initiate transcription (Dellino et al, 2004).…”

Linking the epigenetic ‘language’ of covalent histone modifications to cancer

“…(1) The PcG complex that contains EED and enhancer of zeste homolog (EZH) proteins 1 and 2 recruits HDACs and represses transcription of target genes by the combinatory action of local histone methylation and deacetylation. (2) The Polycomb repressive complex 1 (PRC-1) contains polycomb 2 (HPC2), polyhomeotic (HPH), BM1 and Ring-finger protein 1 (RING1) proteins and associates with the SWI/SNF chromatin remodelling complex, and negatively regulates chromatin accessibility (Shao et al, 1999).…”

PHC3, a component of the hPRC-H complex, associates with 2A7E during G0 and is lost in osteosarcoma tumors

“…First identified in Drosophila (Lewis, 1978), they have been found throughout higher eucaryotes. PcG complexes are responsible for longterm silencing of genes by altering chromatin structure through deacetylation of histone tails and by inhibiting ATP-dependent chromatin remodeling (Shao et al, 1999;van der Vlag and Otte, 1999).…”

“…The first complex, which includes homologues of the Drosophila esc and E(z) genes, has histone deacetylase activity (Sewalt et al, 1998;van Lohuizen et al, 1998). The second PcG complex (dPRC-1 in Drosophila, mPRC1 in mice and hPRC-H in humans) contains homologues of the Drosophila Pc, Psc, Ph, RING and Scm genes (Franke et al, 1992;Alkema et al, 1997;Satijn et al, 1997;Shao et al, 1999) and can mediate silencing of target genes by interfering with SWI/Snf chromatin remodeling machinery, blocking transcriptional initiation and the recruitment of additional silencing activities (Shao et al, 1999;Francis et al, 2001;King et al, 2002;Levine et al, 2002;Dellino et al, 2004;Lavigne et al, 2004).…”