Polycomb Silencing Blocks Transcription Initiation

Dellino, Gaetano Ivan; Schwartz, Yuri B.; Farkas, Gabriella; McCabe, Donna; Elgin, Sarah C. R.; Pirrotta, Vincenzo

doi:10.1016/s1097-2765(04)00128-5

Cited by 251 publications

(178 citation statements)

References 29 publications

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“…Protein interactions have been shown to be mediated through the SAM domain (Ph) and the RING domain (RING and Bmi1), which may also play a critical role in recruitment (Levine et al, 2002;Lavigne et al, 2004). Studies have shown that the PRC1 complex does not significantly alter nucleosomal position or access of nucleases to the nucleosomal arrays (Dellino et al, 2004;Lavigne et al, 2004). This suggests that the PRC1 complex can inhibit chromatin remodeling by blocking interaction with SWI/Snf without making the template inaccessible.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6 showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G 0 . Previous loss of heterozygosity (LoH) analyses had shown that the region containing PHC3 underwent frequent LoH in primary human osteosarcoma tumors. When we examined normal bone and human osteosarcoma tumors, we found loss of PHC3 expression in 36 of 56 osteosarcoma tumors. Sequence analysis revealed that PHC3 was mutated in nine of 15 primary osteosarcoma tumors. These findings suggest that loss of PHC3 may favor tumorigenesis by potentially disrupting the ability of cells to remain in G 0 .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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“…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).…”

Section: Maintenance Of Hox Expression Patternmentioning

confidence: 99%

Epigenetic regulations in hematopoietic Hox code

Hua

Yan

2010

Oncogene

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“…H2A ubiquitylation is carried out by PRC1 (13,19), which is targeted to chromatin through the recognition of H3 Lys-27 trimethylation by chromodomain-containing PcG subunits (18,20), such as M33/ Cbx2 or Pc2/Cbx4 (21). Once bound to chromatin, PcG complexes repress transcription by one or more mechanisms, including interference with nucleosome remodeling by the Swi/Snf complex chromatin remodeling (19) and/or with transcription initiation (22).…”

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confidence: 99%

Proteomics Analysis of Ring1B/Rnf2 Interactors Identifies a Novel Complex with the Fbxl10/Jhdm1B Histone Demethylase and the Bcl6 Interacting Corepressor

Sánchez

Demmers³

et al. 2007

Molecular & Cellular Proteomics

206

190

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Ring1B/Rnf2 is a RING finger protein member of the Polycomb group (PcG) of proteins, which form chromatinmodifying complexes essential for embryonic development and stem cell renewal and which are commonly deregulated in cancer. Ring1B/Rnf2 is a ubiquitin E3 ligase that catalyzes the monoubiquitylation of the histone H2A, one of the histone modifications needed for the transcriptional repression activity of the PcG of proteins. Ring1B/Rnf2 was shown to be part of two complexes, the PRC1 PcG complex and the E2F6.com-1 complex, which also contains non-PcG members, thus raising the prospect for additional Ring1B/Rnf2 partners and functions extending beyond the PcG. Here we used a high throughput proteomics approach based on the single step purification, using streptavidin beads, of in vivo biotinylated Ring1B/Rnf2 and associated proteins from a nuclear extract from erythroid cells and their identification by mass spectrometry. About 50 proteins were confidently identified of which 20 had not been identified previously as subunits of Ring1B/Rnf2 complexes. We found that histone demethylases LSD1/Aof2 and Fbxl10/Jhdm1B, casein kinase subunits, and the BcoR corepressor were among the new interactors identified. We also isolated an Fbxl10/Jhdm1B complex by biotinylation tagging to identify shared interacting partners with Ring1B/Rnf2. In this way we identified a novel Ring1B-Fbxl10 complex that also includes Bcl6 corepressor (BcoR), CK2␣, Skp1, and Nspc1/Pcgf1. The putative enzymatic activities and protein interaction and chromatin binding motifs present in this novel Ring1B-Fbxl10 complex potentially provide additional mechanisms for chromatin modification/recruitment to chromatin and more evidence for Ring1B/Rnf2 activities beyond those typically associated with PcG function. Lastly this work demonstrates the utility of biotinylation tagging for the rapid characterization of complex mixtures of multiprotein complexes achieved through the iterative use of this simple yet high throughput proteomics approach.Molecular & Cellular Proteomics 6:820 -834, 2007.In multicellular organisms, cell identity is controlled, at least in part, by epigenetic events, including DNA methylation and post-translational modifications of histones that lead to chromatin structure regulation (1). These modifications are carried out by protein complexes recruited through DNA sequences and/or specific recognition of modified histones. The Polycomb group (PcG) 1 of proteins, first identified genetically as regulators of Hox genes in the fly Drosophila melanogaster (for a review, see Ref. 2), is an example of such a complex. PcG functions cover many aspects of vertebrate development and tissue homeostasis by preventing the inappropriate activation of many transcription factor-coding genes and other genes involved in cell signaling and cell proliferation (3-7). Currently it is believed that PcG proteins play a role in setting the balance between proliferation and differentiation in normal development. Deregulation of PcG proteins disrupts such a ba...

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Polycomb Silencing Blocks Transcription Initiation

Cited by 251 publications

References 29 publications

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

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

Epigenetic regulations in hematopoietic Hox code

Proteomics Analysis of Ring1B/Rnf2 Interactors Identifies a Novel Complex with the Fbxl10/Jhdm1B Histone Demethylase and the Bcl6 Interacting Corepressor

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