PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes

Gao, Zhonghua; Zhang, Jin; Bonasio, Roberto; Strino, Francesco; Sawai, Ayana; Parisi, Fulvio; Kluger, Yuval; Reinberg, Danny

doi:10.1016/j.molcel.2012.01.002

Cited by 771 publications

(1,256 citation statements)

References 44 publications

(77 reference statements)

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“…The PRC2 catalyzed H3K27me3 mark constitutes a docking site for Cbx proteins, which are subunits of PRC1 and mediate its recruitment to chromatin. 8,9 In mouse embryonic stem cells (mESCs) Cbx7 is the prevalent Cbx protein that controls the expression of key developmental genes during pluripotency. In the course of differentiation Cbx7 is replaced by other proteins of the Cbx family (Cbx2 and Cbx4), which play a role in later stages of development.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Mediator is considered an enhancer of RNA-Polymerase II dependent transcription but its function and regulation in pluripotent mouse embryonic stem cells (mESCs) remains unresolved. One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to the core Mediator. Here we report that Med12 operates together with PRC1 to silence key developmental genes in pluripotency. At the molecular level, while PRC1 represses genes it is also required to assemble ncRNA containing Med12-Mediator complexes. In the course of cellular differentiation the H2A ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the association of Cdk8 with Mediator. This remodeling of Mediator-associated protein complexes converts Mediator from a transcriptional repressor to a transcriptional enhancer, which then mediates ncRNA-dependent activation of Polycomb target genes. Altogether, our data reveal how the interplay of PRC1, ncRNA and Mediator complexes controls pluripotency and cellular differentiation.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…12,20 However, a systematic proteomics approach in human cells identified additional non-canonical PRC1 complexes, revealing a greater complexity than previously anticipated. 13 While RING1A/1B is a common theme for all PRC1 complexes, CBX and PHC proteins are replaced by either RYBP or YAF-2 in non-canonical PRC1 complexes. The incorporation of either RYBP or YAF-2 into PRC1 is presumably of functional relevance since-at least in vitro-RYBP can stimulate the ubiquitylation activity of PRC1 but YAF-2 does not.…”

Section: Introductionmentioning

confidence: 99%

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

Eid

Torres-Padilla

2016

Epigenetics

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An intense period of chromatin remodeling takes place after fertilization in mammals, which is thought necessary for epigenetic reprogramming to start a new developmental program. While much attention has been given to the role of Polycomb Repressive Complex 2 (PRC2) and to canonical PRC1 complexes during this process, little is known as to whether there is any contribution of non-canonical PRC1 in shaping the chromatin landscape after fertilization. Here, we first describe in detail the temporal dynamics and abundance of H2A ubiquitylation (H2AK119ub), a histone modification catalyzed by PRC1, during preimplantation mouse development. In addition, we have analyzed the presence of the 2 characteristic subunits of non-canonical PRC1 complexes, RYBP and its homolog YAF-2. Our results indicate that H2AK119ub is inherited from the sperm, rapidly removed from the paternal chromatin after fertilization, but detected again prior to the first mitosis, suggesting that PRC1 activity occurs as early as the zygotic stage. RYBP and YAF-2, together with the non-canonical subunit L3MBTL2, are all present during preimplantation development but show different temporal dynamics. While RYBP is absent in the zygote, it is strongly induced from the 4-cell stage onwards. YAF-2 is inherited maternally and localizes to the pericentromeric regions in the zygote, is strongly induced between the 2-and 4-cell stages but then remains weak to undetectable subsequently. All together, our data suggest that non-canonical PRC1 is active during pre-implantation development and should be regarded as an additional component during epigenetic reprogramming and in the establishment of cellular plasticity of the early embryo.

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“…Subsequently, PRC1 monoubiquitylates histone H2A on lysine 119 (H2AK119) to induce transcriptional repression. A recent proteomics study led to the classification of six groups of PRC1 complexes (6). Each of these groups was further categorized as either canonical or noncanonical PRC1 complexes.…”

Section: The Bcor Complex Is a Distinct Subtype Of Prc1mentioning

confidence: 99%

“…Only canonical PRC1 complexes are targeted to H3K27me3-enriched genome regions through the CBX subunit (6). On the other hand, the BCOR complex is categorized into a noncanonical PRC1 subgroup called PRC1.1 (6).…”

Section: The Bcor Complex Is a Distinct Subtype Of Prc1mentioning

confidence: 99%

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Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers

Yamamoto

Abe

Emi

2014

Molecular Cancer Research

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The dysregulation of proper transcriptional control is a major cause of developmental diseases and cancers. Polycomb proteins form chromatin-modifying complexes that transcriptionally silence genome regions in higher eukaryotes. The BCL6 corepressor (BCOR) complex comprises ring finger protein 1B (RNF2/RING1B), polycomb group ring finger 1 (PCGF1), and lysine-specific demethylase 2B (KDM2B) and is uniquely recruited to nonmethylated CpG islands, where it removes histone H3K36me2 and induces repressive histone H2A monoubiquitylation. Germline BCOR mutations have been detected in patients with oculofaciocardiodental and Lenz microphthalmia syndromes, which are inherited conditions. Recently, several variants of BCOR and BCORlike 1 (BCORL1) chimeric fusion transcripts were reported in human cancers, including acute promyelocytic leukemia, bone sarcoma, and hepatocellular carcinoma. In addition, massively parallel sequencing has identified inactivating somatic BCOR and BCORL1 mutations in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, medulloblastoma, and retinoblastoma. More importantly, patients with AML and MDS with BCOR mutations exhibit poor prognosis. This perspective highlights the detection of BCOR mutations and fusion transcripts of BCOR and BCORL1 and discusses their importance for diagnosing cancer subtypes and estimating the treatment responses of patients. Furthermore, this perspective proposes the need for additional functional studies to clarify the oncogenic mechanism by which BCOR and BCORL1 are disrupted in cancers, and how this may lead to the development of novel therapeutics. Mol Cancer Res; 12(4); 479-84. Ó2014 AACR. IntroductionA major cause of developmental diseases and cancers is the dysregulation of proper transcriptional control, a process that is directly regulated by transcription factors, coactivators, and corepressors. Till date, several hundred transcriptional coregulators have been reported in the literature. Recently, the increased use of massively parallel sequencing techniques has expanded our knowledge on the induction of congenital diseases and cancers caused by specific gene mutations.

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PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes

Cited by 771 publications

References 44 publications

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

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

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

Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers

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