Composition, recruitment and regulation of the PRC2 complex

Nayak, Vinod; Xu, Chao; Min, Jinrong

doi:10.4161/nucl.2.4.16266

Cited by 14 publications

(12 citation statements)

References 55 publications

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“…PRC2, which is required for the initial targeting of genomic regions to be silenced, contains three core subunits, although other proteins, transiently interacting with the core, have been described. 28 The three core subunits of PRC2 are the histone methyltransferase (HMT) catalytic subunit EZH2, the zinc finger protein Suz12, and EED (embryonic ectoderm development), the subunit involved in substrate recognition. 29 PRC1, on the other hand, is required for stabilizing the gene silencing initiated by PRC2, and is a much more heterogeneous complex with several different forms identified in mammals, characterized by different subunit paralogues, composition and function.…”

Section: Lncrnas In X-chromosome Inactivation: Decoys and Guides For mentioning

confidence: 99%

Long non-coding RNAs and chromatin modifiers

Marchese¹,

Huarte²

2013

Epigenetics

164

117

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Section: Lncrnas In X-chromosome Inactivation: Decoys and Guides For mentioning

confidence: 99%

Long non-coding RNAs and chromatin modifiers

Marchese¹,

Huarte²

2013

Epigenetics

164

117

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“…SUZ12 occupancy is a Surrogate for polycomb-repressor complex 2 occupancy and in embryonic stem cells this has been shown to associate with transcriptional repression of hypermethylated loci (6, 18). Consistent with this, we observed an increase in SUZ12 occupied sites with increasing CIMP cluster (P<0.0001, Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

“…Polycomb occupancy was inferred from SUZ12 CHIP-Seq data from hESCl cells analysed as part of the ENCODE consortium (59). SUZ12 was chosen as a Surrogate for PRC2 occupancy as previous studies indicate that it is an essential subunit of the PRC2 complex (18, 60). The overlap function within BedTools (61) was used to overlap differentially methylated probes within each cluster versus normal with regions where SUZ12 was bound in hESCl cells, producing a list of regions where methylation and PRC2 occupancy co-occurred.…”

Section: Methodsmentioning

confidence: 99%

Genome Scale Epigenetic Profiling Reveals Five Distinct Subtypes of Colorectal Cancer

Fennell

Dumenil

Härtel

et al. 2018

Preprint

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BACKGROUND:Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.RESULTSAn unselected cohort of 216 colorectal cancers clustered into five clinically and molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High cancers were most frequent in the proximal colons of female patients. These dichotomised into CIMP-Hl and CIMP-H2 based on methylation profile which was supported by over representation of BRAF (74%, P<0.0001) or KRAS (55%, P<0.0001) mutation, respectively. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CI MP-Negative subgroup to 75 years in the CIMP-Hl subgroup (P<0.0001). There was a striking association between PRC2-marked loci and those subjected to significant gene body methylation in CIMP-type cancers (P<1.6xl078). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for genes involved in chromatin remodelling, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality.CONCLUSIONThere are five clinically and molecularly distinct subgroups of colorectal cancer based on genome wide epigenetic profiling. These analyses highlighted an unidentified role for gene body methylation in progression of serrated neoplasia. Subgroup-specific mutation of distinct epigenetic regulator genes revealed potentially druggable vulnerabilities for these cancers, which may provide novel precision medicine approaches.

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“…As a histone binding component of many histone modification complexes and chromatin remodeling complexes, Rbbp7 has been proposed to perform its function through affecting complexes activity and regulating the substrate specificity [28,55]. For example, Rbbp7 was reported to be essential for enzymatic activity of histone acetyltransferase Hat1, and its substrate recognition.…”

Section: Discussionmentioning

confidence: 99%

Rbbp7 Is Required for Uterine Stromal Decidualization in Mice1

Kong

Liu

et al. 2015

Biology of Reproduction

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Uterine stromal cells undergo extensive proliferation and differentiation during postimplantation development, a process known as decidualization. While a range of signaling molecules have been demonstrated to play essential roles in this event, its potential epigenetic regulatory mechanisms remain largely unknown. Retinoblastoma binding protein 7 (Rbbp7) is a protein reported as a core component of many histone modification and chromatin remodeling complexes. In the present study, our in situ hybridization and immunochemistry analysis first reveals a spatiotemporal expression of Rbbp7 in the uterus during the peri-implantation period. Observations of remarkable induction of Rbbp7 expression in uterine stromal cells in response to progesterone-nuclear receptor PR signaling point to its potential physiological significance during postimplantation uterine development. Employing a stealth RNA knockdown approach, combined with primary murine uterine stromal cell culture and an in vitro-induced decidualization model, we further demonstrate that Rbbp7 silencing compromises stromal cell decidualization via attenuating histone H4 acetylation and cyclin D3 expression. The results collectively suggest that Rbbp7 is a potentially functional player regulating normal histone acetylation modification and cyclin D3 expression in stromal cells during postimplantation decidual development.

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Composition, recruitment and regulation of the PRC2 complex

Cited by 14 publications

References 55 publications

Long non-coding RNAs and chromatin modifiers

Long non-coding RNAs and chromatin modifiers

Genome Scale Epigenetic Profiling Reveals Five Distinct Subtypes of Colorectal Cancer

Rbbp7 Is Required for Uterine Stromal Decidualization in Mice1

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