Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Polycomb repression of Hox genes involves spatial feedback but not domain compaction or phase-transition

ABSTRACT: Polycomb group proteins play a critical role in silencing transcription during development. It is commonly proposed that Polycomb dependent changes in genome folding, which compact chromatin, contribute directly to repression by blocking binding of activating complexes. Recently, it has also been argued that liquid-liquid demixing of Polycomb proteins facilitates this compaction and repression by phase-separating target genes into a membraneless compartment. To test these models, we utilized Optical Reconstruction of Chromatin Architecture (ORCA) to trace the Hoxa gene cluster, a canonical Polycomb target, in thousands of single cells. Across multiple cell types, we find that Polycomb-bound chromatin frequently explores decompact states and partial mixing with neighboring chromatin, while remaining uniformly repressed, challenging the repression-by-compaction or phase-separation models. Using polymer simulations, we show that these observed flexible ensembles can be explained by “spatial feedback”: transient contacts that contribute to propagation of the epigenetic state, (epigenetic memory) without inducing a globular organization.

ORGANISM(S): Mus musculus

PROVIDER: GSE237501 | GEO | 2024/02/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

HP1β dependent phase separation regulates embryonic stem cells exit from naïve pluripotent state

Project description:Liquid-liquid phase separation has drawn great attention as a physical process that mediates the formation of membraneless organelles in cells to coordinate biological reactions in space and time. Previously, it was proposed that the formation of phase-separated droplets is a unique property of HP1α. Here, we show that HP1β, but not HP1α and HP1ɤ, forms nucleosome dependent phase separated droplets. We demonstrate that H3K9me3 is required for HP1β dependent phase separation. Importantly, HP1β dependent phase separation regulates heterochromatin formation, thus controlling embryonic stem cells differentiation. In response to pluripotency exit, HP1β is phosphorylated at serine 89 recruiting KAP1, a pluripotency regulator, and sequestering it in the heterochromatin compartment. This induces changes in the level of pluripotency factors and triggers pluripotency exit. We propose that such a trapping mechanism creates a fast and dynamic mode of remote control of gene expression to regulate cell fate decisions solely based on membraneless organelles.

2022-05-01 | E-MTAB-8329 | biostudies-arrayexpress

Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops

Project description:Polycomb-repressive complex 1 (PRC1) has a constraining influence on 3D genome organization, mediating localized and chromosome-wide clustering of target loci. Polycomb-bound regions form transcriptionally repressive chromatin domains independent of topologically associating domains (TADs). Several subunits of PRC1 have the capacity to form biomolecular condensates through liquid-liquid phase separation (LLPS) in vitro and when tagged and over-expressed in cells. Here, we use 1,6 hexandiol (1,6-HD), which disrupts liquid-like condensates, to examine the role of endogenous PRC1 biomolecular condensates on local and chromosome-wide clustering of PRC1-bound loci. Using imaging and chromatin immunoprecipitation combined with deep sequencing (ChIP-seq) analyses, we show that PRC1-mediated localized chromatin compaction and clustering of targeted genomic loci at megabase and tens of megabase scales can be reversibly disrupted by the addition and subsequent removal of 1,6-HD to mouse embryonic stem cells (mESCs). Decompaction and dispersal of polycomb domains and clusters cannot be solely attributable to the reduction of PRC1 binding following 1,6-HD treatment as the addition of 2,5-HD has similar effects despite this alcohol not perturbing PRC1-mediated clustering, at least at the sub-megabase and megabase scales. These results suggest that weak, hydrophobic interactions between PRC1 molecules characteristic of liquid condensates do have a role in polycomb-mediated genome organization.

2023-02-13 | GSE224930 | GEO

A Polycomb domain found in committed cells impairs differentiation when introduced into PRC1 in pluripotent cells (EBs/NPCs RNA-seq datasets)

Project description:The CBX family of proteins is central to proper mammalian development via key roles in Polycomb-mediated maintenance of repression. CBX proteins in differentiated lineages have chromatin compaction and phase separation activities that might contribute to maintaining repressed chromatin. The predominant CBX protein in pluripotent cells, CBX7, lacks the domain required for these activities. We inserted this functional domain into CBX7 in embryonic stem cells to test the hypothesis that it contributes a key epigenetic function. ESCs expressing this chimeric CBX7 were impaired in their ability to properly form embryoid bodies and neural progenitor cells and showed reduced activation of lineage-specific genes across differentiation. Neural progenitors exhibited a corresponding inappropriate maintenance of Polycomb binding at neural-specific loci over the course of differentiation. We propose that a switch in the ability to compact and phase separate is a central aspect of Polycomb group function during the transition from pluripotency to differentiated lineages.

2021-10-11 | GSE151900 | GEO

A Polycomb domain found in committed cells impairs differentiation when introduced into PRC1 in pluripotent cells (ChIP-seq, CUT&RUN datasets)

2021-10-11 | GSE151899 | GEO

Polycomb repression of Hox genes involves spatial feedback but not domain compaction or phase-transition

Project description:Polycomb repression of Hox genes involves spatial feedback but not domain compaction or phase-transition

| PRJNA995536 | ENA

PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking (RNA-Seq)

Project description:The Polycomb repression machinery in Drosophila comprises PRC1 that monoubiquitinates histone H2A at lysine 118 (H2Aub1) and PR-DUB, a major H2Aub1 deubiquitinase, but how H2Aub1 levels must be balanced for Polycomb repression remains enigmatic. We show that H2Aub1 is enriched at Polycomb target genes in early embryos but depleted from these genes during developmental stages when PRC1 represses their transcription. Accordingly, Polycomb targets remain repressed in H2Aub1-deficient animals. In PR-DUB catalytic mutants, high-level H2Aub1 accumulation at Polycomb targets increases chromatin accessibility, consistent with disruption of chromatin fiber folding by H2Aub1 in vitro. Consequently, PR-DUB mutants show defective Polycomb repression, while general transcription is largely unperturbed by the genome-wide, low-level H2Aub1 increase. Changes in H2Aub1 levels alter H3K27 methylation-kinetics but PRC2 nevertheless generates canonical H3K27me3 domains in PRC1 or PR-DUB catalytic mutants. PR-DUB therefore acts as a rheostat that removes excessive H2Aub1 that, though deposited by PRC1, antagonizes PRC1-mediated chromatin compaction.

2022-11-09 | GSE210235 | GEO

PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking (ChIP-Seq)

2022-11-09 | GSE210233 | GEO

PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking (ATAC-Seq)

2022-11-09 | GSE210232 | GEO

Polycomb-mediated chromatin compaction during cell differentiation

Project description:Polycomb-mediated chromatin compaction during cell differentiation

| PRJNA354285 | ENA

Characterization of human erythroid chromatin in a two-phase liquid differentiation system

Project description:A two-phase liquid differentiation of peripheral blood mononuclear cells (PBMC) can be used to study human erythroid cells. To determine the epigenetic landscape of erythroid cells derived from PBMC we have performs ChIP-seq for histone marks associated with promoters (H3K4me3), enhancers (H3K4me1) and polycomb repression (H3K27me3) as well as for chromatin bound pol2. In addition we characterized the binding of the boundary element CTCF and key erythroid transcription factors NF-E2 and SCL/TAL.

2020-06-29 | GSE125753 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data