Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2

Cooper, Sarah; Grijzenhout, Anne; Underwood, E.; Ancelin, Katia; Zhang, Tianyi; Nesterova, Tatyana B.; Anil-Kirmizitas, Burcu; Bassett, Andrew; Kooistra, Susanne M.; Agger, Karl; Helin, Kristian; Heard, Edith; Brockdorff, Neil

doi:10.1038/ncomms13661

Cited by 230 publications

(296 citation statements)

References 42 publications

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“…Surprisingly, they discovered a small but significant inhibitory effect of H2Aub on H3K27 trimethylation by PRC2 in vitro , which could not be readily explained. In a subsequent study, two additional protein components Jarid2–Aebp2 (Jumonji And AT-Rich Interaction Domain Containing 2-Adipocyte Enhancer-Binding Protein 2) were found to bind PRC2 and stimulate its activity ~25-fold on nucleosomes containing H2Aub (Figure 4) [50]. This confirmed the initially proposed crosstalk between PRC1 and PRC2, and indicated that its associated proteins modulate PRC2 function.…”

Section: Biochemical Crosstalk Between H2aub and H3k27me3supporting

confidence: 70%

Studies of biochemical crosstalk in chromatin with semisynthetic histones

Leonen

Upadhyay

Chatterjee

2018

Current Opinion in Chemical Biology

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Reversible post-translational modifications of histone proteins in eukaryotic chromatin are closely tied to gene function and cellular development. Specific combinations of histone modifications, or marks, are implicated in distinct DNA-templated processes mediated by a range of chromatin-associated enzymes that install, erase and interpret the histone code. Mechanistic studies of the precise biochemical relationship between sets of marks and their effects on chromatin function are significantly complicated by the dynamic nature and heterogeneity of marks in cellular chromatin. Protein semisynthesis is a chemical technique that enables the piecewise assembly of uniformly and site-specifically modified histones in quantities sufficient for biophysical and biochemical analyses. Recent pioneering efforts in semisynthesis have yielded access to histones site-specifically modified by entire proteins, such as ubiquitin (Ub) and the small ubiquitin-like modifier (SUMO). Herein, we highlight key studies of biochemical crosstalk involving Ub and SUMO in chromatin that were enabled by histone semisynthesis.

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Section: Biochemical Crosstalk Between H2aub and H3k27me3supporting

confidence: 70%

Studies of biochemical crosstalk in chromatin with semisynthetic histones

Leonen

Upadhyay

Chatterjee

2018

Current Opinion in Chemical Biology

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“…Indeed, Jarid2 may bind to PRC1-mediated H2AK119Ub, thus enabling PRC2 to become recruited. However, the situation may be complex, with multiple parallel pathways for PRC2 and PRC1 recruitment to the Xi 51 .…”

Section: Factors Associated With Prc1 and 2 Complexesmentioning

confidence: 99%

X chromosome inactivation: new players in the initiation of gene silencing

Pinheiro

Heard

2017

F1000Res

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X chromosome inactivation (XCI) is a dosage compensation process that was adopted by female mammals to balance gene dosage between XX females and XY males. XCI starts with the upregulation of the non-coding RNA Xist, after which most X-linked genes are silenced and acquire a repressive chromatin state. Even though the chromatin marks of the inactive X have been fairly well described, the mechanisms responsible for the initiation of XCI remain largely unknown. In this review, we discuss recent developments that revealed unexpected factors playing a role in XCI and that might be of crucial importance to understand the mechanisms responsible for the very first steps of this chromosome-wide gene-silencing event.

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“…It is well established that the N-terminal domain of JARID2 is needed for its interaction with EZH2 and its recruitment to chromatin (Son et al, 2013;Kaneko et al, 2014a;Sanulli et al, 2015;Cooper et al, 2016;Chen et al, 2018). By contrast, the C-terminal of JARID2 has not been studied in detail.…”

Section: Discussionmentioning

confidence: 99%

A novel form of JARID2 is required for differentiation in lineage‐committed cells

et al. 2018

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Polycomb repressive complex‐2 (PRC2) is a group of proteins that play an important role during development and in cell differentiation. PRC2 is a histone‐modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co‐factor of PRC2 and is important for targeting PRC2 to chromatin. Here, we show that, unlike in embryonic stem cells, in lineage‐committed human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N‐terminal PRC2‐interacting domain (ΔN‐JARID2). We show that ΔN‐JARID2 is a cleaved product of full‐length JARID2 spanning the C‐terminal conserved jumonji domains. JARID2 knockout in keratinocytes results in up‐regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID2‐null keratinocytes can be rescued by expression of ΔN‐JARID2 suggesting that, in contrast to PRC2, ΔN‐JARID2 promotes activation of differentiation genes. We propose that a switch from expression of full‐length JARID2 to ΔN‐JARID2 is important for the up‐regulation differentiation genes.

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Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2

Cited by 230 publications

References 42 publications

Studies of biochemical crosstalk in chromatin with semisynthetic histones

Studies of biochemical crosstalk in chromatin with semisynthetic histones

X chromosome inactivation: new players in the initiation of gene silencing

A novel form of JARID2 is required for differentiation in lineage‐committed cells

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