Loss- and gain-of-function mutations show a Polycomb group function for Ring1A in mice

Lorente, Mar; Marcos-Gutierrez, Camelia V.; Pérez, Cirilo; Schoorlemmer, Jon; Ramirez, A. I.; Magin, Thomas M.; Vidal, Miguel

doi:10.1242/dev.127.23.5093

Cited by 154 publications

(18 citation statements)

References 52 publications

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“…1a), raising the possibility that PRC1 functions in POT. To determine the function of PRC1 in POT, PRC1 function was eliminated after embryonic day 15 (E15) using Ddx4-Cre 32 to mutate the E3 ubiquitin ligase RNF2 on a background lacking its partially redundant paralog RING1 (RING1A) to create PRC1 conditional knockout (PRC1cKO) mice 12,[33][34][35] (Fig. 1b).…”

Section: Resultsmentioning

confidence: 99%

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PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Yeh

Munakata

et al. 2022

Nat Commun

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The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.

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Section: Resultsmentioning

confidence: 99%

“…Mice were maintained on a mixed genetic background of FVB and C57BL/6 J. Generation of mutant Ring1 ( Ring1 −/− ) and Rnf2 floxed alleles ( Ring1 F/F ) were reported previously 34 , 71 . Ring1 −/− and Ring1 F/F mice were obtained from Dr. Haruhiko Koseki.…”

Section: Methodsmentioning

confidence: 99%

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Yeh

Munakata

et al. 2022

Nat Commun

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“…Eed flox/flox mice were kindly provided by Dr. Weipeng Mu and Dr. Terry Magnuson (Mu et al 2014). Ring1a −/− and Ring1b flox/flox mice were previously described (del Mar Lorente et al 2000), and were kindly provided by Dr. Miguel Vidal. Both male and female mice were used in this study.…”

Section: Micementioning

confidence: 99%

Polycomb complexes redundantly maintain epidermal stem cell identity during development

et al. 2021

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Polycomb repressive complex 1 (PRC1) and PRC2 are critical epigenetic developmental regulators. PRC1 and PRC2 largely overlap in their genomic binding and cooperate to establish repressive chromatin domains demarcated by H2AK119ub and H3K27me3. However, the functional contribution of each complex to gene repression has been a subject of debate, and understanding of its physiological significance requires further studies. Here, using the developing murine epidermis as a paradigm, we uncovered a previously unappreciated functional redundancy between Polycomb complexes. Coablation of PRC1 and PRC2 in embryonic epidermal progenitors resulted in severe defects in epidermal stratification, a phenotype not observed in the single PRC1-null or PRC2-null epidermis. Molecular dissection indicated a loss of epidermal identity that was coupled to a strong derepression of nonlineage transcription factors, otherwise repressed by either PRC1 or PRC2 in the absence of its counterpart. Ectopic expression of subsets of PRC1/2-repressed nonepidermal transcription factors in wild-type epidermal stem cells was sufficient to suppress epidermal identity genes, highlighting the importance of functional redundancy between PRC1 and PRC2. Altogether, our studies show how PRC1 and PRC2 function as two independent counterparts, thereby providing a repressive safety net that protects and preserves lineage identity.

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“…Recent studies identified an important role for PRC2 in restricting trophoblast induction in human naïve pluripotent stem cells in vitro [ 57 , 58 ], suggesting a role in the earliest mammalian lineage decision after fertilization. In PRC1, the loss of RING1B protein results in developmental arrest at E6.5, during gastrulation, but RING1A mutants were able to survive and reach birth, although displaying defects in transformation of the axial skeleton and altered levels of Hox gene expression [ 59 , 60 ].…”

Section: Roles Of Polycomb Group Proteins In Pluripotency and Early D...mentioning

confidence: 99%

The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development

Loh

Veenstra

2022

Epigenomes

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Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development.

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Loss- and gain-of-function mutations show a Polycomb group function for Ring1A in mice

Cited by 154 publications

References 52 publications

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Polycomb complexes redundantly maintain epidermal stem cell identity during development

The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development

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