RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells

Hisada, Kaori; Sánchez, Carmen; Endo, Takaho A.; Endoh, Mitsuhiro; Román-Trufero, Mónica; Sharif, Jafar; Koseki, Haruhiko; Vidal, Miguel

doi:10.1128/mcb.06441-11

Cited by 81 publications

(89 citation statements)

References 64 publications

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“…For example, non-canonical PRC1 ligases could have an expanded list of client substrates and if so, it might explain why they have not maintained optimal binding to the nucleosome surface. The requirement for non-canonical PRC1 complexes in ES cell proliferation 62 , retroviral repression 63 , and regulation of metabolic genes and cell cycle progression 25 may be consistent with a need for greater flexibility (faster intrinsic rate, lower affinity for substrate) compared with the action of canonical PRC1 during development (where precision may be of paramount importance). The recent rapid progress in this area suggests that important elements of PCGF-RING1 E3 ligase function and regulation may yet be discovered.…”

Section: Discussionmentioning

confidence: 85%

BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase

Taherbhoy

Huang²,

Cochran³

2015

Nat Commun

102

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Polycomb repressive complex 1 (PRC1) is required for ubiquitination of histone H2A lysine 119, an epigenetic mark associated with repression of genes important in developmental regulation. The E3 ligase activity of PRC1 resides in the RING1A/B subunit when paired with one of six PCGF partners. The best known of these is the oncogene BMI1/PCGF4. We find that canonical PRC1 E3 ligases such as PCGF4-RING1B have intrinsically very low enzymatic activity compared with non-canonical PRC1 RING dimers. The structure of a high-activity variant in complex with E2 (PCGF5-RING1B-UbcH5c) reveals only subtle differences from an earlier PCGF4 complex structure. However, two charged residues present in the modelled interface with E2-conjugated ubiquitin prove critical: in BMI1/PCGF4, these residues form a salt bridge that may limit efficient ubiquitin transfer. The intrinsically low activity of the PCGF4-RING1B heterodimer is offset by a relatively favourable interaction with nucleosome substrates, resulting in an efficient site-specific monoubiquitination.

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Section: Discussionmentioning

confidence: 85%

BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase

Taherbhoy

Huang²,

Cochran³

2015

Nat Commun

102

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“…This observation was surprising given the expected nuclear localization of RYBP based on findings in other cell types. 15,37 However, immediately after fertilization, we did not detect RYBP at the zygote stage, neither in the cytoplasm nor in the nucleoplasm of any of the 2 pronuclei ( Fig. 2A).…”

Section: H2ak119 Monoubiquitination Is Dynamic During Preimplantationmentioning

confidence: 78%

“…Double knockout of Rybp and Yaf2 in ES cells showed no synergistic effects, suggesting potential independent effects for these 2 forms of noncanonical PRC1 complexes. 15 At later stages of development, at the blastocyst stage, previous data suggested a lack of enrichment of CBX2 at RING1B/ RNF2 foci in the blastocyst. 25 We observed foci of H2AK119ub at this stage, which are presumably linked to X inactivation.…”

Section: Discussionmentioning

confidence: 97%

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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“…Other components of PRC1, such as the Cbx proteins (see below), Rybp and L3mbtl2, are also required for ESC differentiation (Hisada et al, 2012;Morey et al, 2012;Qin et al, 2012;Tavares et al, 2012). Interestingly, ESCs lacking either Ring1B or Eed were still able to form teratomas, but these were found to be smaller, with an increase in the ectodermal or endodermal fraction, respectively (Leeb et al, 2010).…”

Section: Esc Differentiationmentioning

confidence: 99%

“…Non-canonical PRC1 complexes, which contain Rybp (together with additional proteins, such as L3mbtl2 or Kdm2b) rather than the Cbx proteins (Fig. 1D), have recently been described in mammals (García et al, 1999;Trojer et al, 2011;Farcas et al, 2012;Gao et al, 2012;Hisada et al, 2012;Qin et al, 2012;Tavares et al, 2012;He et al, 2013;Wu et al, 2013) (Table 1). At the molecular level, Rybp-PRC1 and Cbx-PRC1 have been shown to regulate different target sets (Morey et al, 2013).…”

mentioning

confidence: 99%

Polycomb complexes in stem cells and embryonic development

2013

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SummaryPolycomb group (PcG) proteins are epigenetic modifiers involved in controlling gene repression. Organized within multiprotein complexes, they regulate developmental genes in multiple cell types and tissue contexts, including embryonic and adult stem cells, and are essential for cell fate transitions and proper development. Here, we summarize recent breakthroughs that have revealed the diversity of PcG complexes acting in different cell types and genomic contexts. Intriguingly, it appears that particular PcG proteins have specific functions in embryonic development, in pluripotent stem cells and in reprogramming somatic cells into a pluripotent-like state. Finally, we highlight recent results from analyzing PcG protein functions in multipotent stem cells, such as neural, hematopoietic and epidermal stem cells. Key words: Polycomb, Stem cells, Transcription, Differentiation, Self-renewal IntroductionAlthough stem cells were discovered decades ago (Till and McCulloch, 1961;Spangrude et al., 1988), their potential as model cells for studying cell differentiation, tissue homeostasis and regeneration has only recently begun to be realized. In particular, embryonic stem cells (ESCs), which are pluripotent cells capable of giving rise to all cell types of the embryo (Boiani and Schöler, 2005), provide a valuable tool for studying embryonic development in vitro.Several transcription factors have been identified as master regulators of pluripotent and multipotent stem cells (Niwa, 2007). Increasing evidence suggests that epigenetic modifications additionally play a crucial role in regulating stem cell characteristics. Among the chromatin modifiers, Polycomb group (PcG) proteins function as gene repressors and are involved in the regulation of stem cell characteristics (Simon and Kingston, 2009). The PcG was originally described as a set of genes responsible for controlling proper body segmentation in Drosophila (Lewis, 1978). During Drosophila embryonic development, PcG proteins repress the homeobox genes of the Hox cluster, thereby determining the proper activation of homeotic genes (Schuettengruber and Cavalli, 2009). The function of PcG proteins as repressors of developmental genes is strongly conserved in mammals (Morey and Helin, 2010). Here, we discuss the latest insights into PcG-mediated epigenetic regulation in stem cells and embryonic development. Molecular activities of PcG complexesIn mammals, PcG proteins are found in several multiprotein complexes (Simon and Kingston, 2009), the best characterized of which are Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) (Margueron and Reinberg, 2011). As epigenetic modifiers, PcG complexes promote gene repression via particular chromatin modifications and compaction (Fig. 1).Here, we provide a brief overview of the molecular mechanisms by which PcG complexes regulate gene expression; for further details, we refer the reader to recent reviews (Lanzuolo and Orlando, 2012;Simon and Kingston, 2013). At the molecular level, PRC2 is responsible for di-and tri-me...

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RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells

Cited by 81 publications

References 64 publications

BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase

BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase

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

Polycomb complexes in stem cells and embryonic development

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