Structure and function of an ectopic Polycomb chromatin domain

De, Sandip; Cheng, Yuzhong; Sun, Miao‐Kun; Gehred, Natalie; Kassis, Judith A.

doi:10.1126/sciadv.aau9739

Cited by 27 publications

(54 citation statements)

References 45 publications

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“…In summary, PcG recruitment in flies is achieved through a network of protein-protein interactions and DNA-binding that tether PRCs to regulatory DNA elements. Rather than a universal hierarchical process, PcG repression involves a mix of cooperative and redundant mechanisms that differ in different contexts (Kassis et al 2017;Brown et al 2018;De et al 2019).…”

Section: Mechanisms Of Recruitment and Formation Of Polycombrepressivmentioning

confidence: 99%

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

2019

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Changes in chromatin structure mediated by ATP-dependent nucleosome remodelers and histone modifying enzymes are integral to the process of gene regulation. Here, we review the roles of the SWI/SNF (switch/sucrose nonfermenting) and NuRD (nucleosome remodeling and deacetylase) and the Polycomb system in chromatin regulation and cancer. First, we discuss the basic molecular mechanism of nucleosome remodeling, and how this controls gene transcription. Next, we provide an overview of the functional organization and biochemical activities of SWI/SNF, NuRD, and Polycomb complexes. We describe how, in metazoans, the balance of these activities is central to the proper regulation of gene expression and cellular identity during development. Whereas SWI/SNF counteracts Polycomb, NuRD facilitates Polycomb repression on chromatin. Finally, we discuss how disruptions of this regulatory equilibrium contribute to oncogenesis, and how new insights into the biological functions of remodelers and Polycombs are opening avenues for therapeutic interventions on a broad range of cancer types.

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Section: Mechanisms Of Recruitment and Formation Of Polycombrepressivmentioning

confidence: 99%

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

2019

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“…Protocol for carrying out ChIP has been described (DE et al 2019). Total PolII [Covance,8WG16,, CP190, and CTCF antibodies were used at 1:100 dilution, anti-H3K27me3 (Millipore, 17-622) and anti-H3K36me3 (Millipore, ABE435) antibodies were used at 1:200 dilution.…”

Section: Chip and Chip-seqmentioning

confidence: 99%

“…ChIP-seq libraries were made with NEBNext® Ultra™ II DNA Library Prep kit. Analysis of the next-generation sequencing data has been described (DE et al 2019). To visualize the distribution of histone modification marks within the transgenes, we created a custom reference gene track by extracting the 400kb sequence surrounding the tou-MiMIC insertion site, 2R:7471605 (Gene Disruption Project database) (VENKEN et al 2011).…”

Section: Chip and Chip-seqmentioning

confidence: 99%

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Defining the Boundaries of Polycomb Domains in Drosophila

Gehred

Fujioka

et al. 2020

Genetics

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Polycomb group (PcG) proteins are an important group of transcriptional repressors that act by modifying chromatin. PcG target genes are covered by the repressive chromatin mark H3K27me3. Polycomb repressive complex 2 (PRC2) is a multiprotein complex that is responsible for generating H3K27me3. In Drosophila, PRC2 is recruited by Polycomb Response Elements (PREs) and then tri-methylates flanking nucleosomes, spreading the H3K27me3 mark over large regions of the genome, the "Polycomb domains". What defines the boundary of a Polycomb domain? There is experimental evidence that insulators, PolII, and active transcription can all form the boundaries of Polycomb domains. Here we divide the boundaries of larval Polycomb domains into six different categories. In one category, genes are transcribed toward the Polycomb domain, where active transcription is thought to stop the spreading of H3K27me3. In agreement with this, we show that introducing a transcriptional terminator into such a transcription unit causes an extension of the Polycomb domain. Additional data suggest that active transcription of a boundary gene may restrict the range of enhancer activity of a Polycomb-regulated gene.

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“…PREs and TREs govern chromatin compaction over broad chromosomal domains, in the order of tens or hundreds of kilobases, by recruiting chromatin modifiers and remodelers. [ 55 ] In the plethora of studies on PcG and TrxG, the chromatin state is evaluated through different histone modifications [ 56–60 ] and the actual chromatin accessibility is not directly examined. It is therefore difficult to reconcile the pattern of local, discrete, and dynamic peaks of accessibility seen at individual enhancers [ 15,29,36 ] with the broad control of chromatin states from PREs and TREs.…”

Section: Enhancer Accessibility Is Controlled At Different Scales Frmentioning

confidence: 99%

Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity

Bozek

Gompel

2020

BioEssays

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Measurements of open chromatin in specific cell types are widely used to infer the spatiotemporal activity of transcriptional enhancers. How reliable are these predictions? In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers. Instead, recent studies focusing on the quantitative nature of accessibility signal reveal subtle differences between active enhancers and their different inactive counterparts: the closed silenced state and the accessible primed and repressed states. While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states. Molecular mechanisms that may account for these quantitative differences are discussed. A model that relates molecular events at an enhancer to changes in its activity and accessibility in a developing tissue is also proposed.

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Structure and function of an ectopic Polycomb chromatin domain

Abstract: Chromatin context influences Polycomb domain structure and function.

Cited by 27 publications

References 45 publications

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

Defining the Boundaries of Polycomb Domains in Drosophila

Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity

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