Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A PRE loop at the dac locus acts as a topological chromatin structure that restricts and specifies enhancer promoter communication

ABSTRACT: 3D genome folding plays a fundamental role for the regulation of developmental genes by facilitating or constraining chromatin interactions between cis-regulatory elements (CREs). Polycomb response elements (PREs) are a specific kind of CREs involved in the memory of transcriptional states in Drosophila melanogaster. PREs act as nucleation sites for Polycomb group (PcG) proteins, which deposit the repressive histone mark H3K27me3, leading to the formation of a class of topologically associating domain (TADs) called Polycomb domains. PREs can establish looping contacts that stabilize gene repression of key developmental genes during development. However, the mechanism by which PRE loops fine tune gene expression is unknown. Using CRISPR/Cas9 genome engineering, we specifically perturbed PRE contacts or enhancer function and used complementary approaches including 4C-seq, Hi-C, and Hi-M to analyze how chromatin architecture perturbation affects gene expression. Our results suggest that the PRE loop at the dac gene locus acts as a constitutive 3D chromatin scaffold during Drosophila development that forms independently of gene expression states and has a versatile function: it restricts enhancer promoter communication and contributes to enhancer specificity.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE247377 | GEO | 2024/06/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of lincRNA genes in human cells

Project description:Characterizing the relationship between genome form and function requires methods both for zooming out, to globally survey the genomic architectural landscape, and for zooming in, to investigate regions of interest at high resolution. High throughput methods based on chromosome conformation capture (3C) have greatly advanced our understanding of the three-dimensional (3D) organization of genomes, but are limited in resolution by their reliance on restriction enzymes. Here we describe a method for comprehensively mapping global chromatin contacts that uses DNaseI for chromatin fragmentation, leading to greatly improved efficiency and resolution. Coupling this method with DNA capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 1,030 lincRNA promoters in two human cell lines, and identified thousands of high-confidence lincRNA promoter-associated chromatin contacts at 1 kilobase pair (kbp) resolution. Detailed analysis of these contacts reveals that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the polycomb repressive complex. Our results provide the first glimpse of the cell-type-specific 3D organization of lincRNA genes. DNase Hi-C assay (x1 replicate) in H1 and K562 cells, respectively. Targeted DNase Hi-C assays of the 220kb promoter-enhancer library (x1 replicate) and the 5Mb lincRNA promoter library (x2 replicate), in H1 and K562 cells, respectively.

2014-11-01 | E-GEOD-56869 | biostudies-arrayexpress

High-resolution mapping defines the cooperative architecture of Polycomb Response Elements

Project description:Polycomb-mediated chromatin repression modulates gene expression during development in metazoans. Binding of multiple sequence-specific factors at discrete Polycomb Response Elements (PREs) is thought to recruit repressive complexes that spread across an extended chromatin domain. To dissect the structure of PREs, we applied high-resolution mapping of non-histone chromatin proteins in native chromatin of Drosophila cells. Analysis of occupied sites reveal cooperative interactions between transcription factors that stabilize Polycomb anchoring to DNA, and implicate the general transcription factor Adf1 as a novel PRE component. By comparing two Drosophila cell lines with differential chromatin states, we provide evidence that repression is accomplished at multiple steps in transcription, including inactivation of distant enhancers, enhanced Polycomb recruitment to PREs and target promoters, and elevated stalling of RNAPII in repressed genes. These results suggest that the stability of complexes bridging promoters, enhancers, and PREs is a crucial aspect of developmentally regulated gene expression. Native chromatin immunoprecipitation of histones, transcription factors and Polycomb protein in Drosophila cell lines.

2014-02-08 | E-GEOD-47829 | biostudies-arrayexpress

High-resolution mapping defines the cooperative architecture of Polycomb Response Elements

2014-02-08 | GSE47829 | GEO

Distinct Polycomb Response Elements control chromatin state and gene activation of the vestigial gene

Project description:Patterned expression of many developmental genes is thought to rely on chromatin-mediated repression. Regulatory DNA sequences called Polycomb Response Elements (PREs) play critical roles in repression. While PREs in transgenes can nucleate trimethylation on lysine 27 of the histone H3 tail (H3K27me3), none have been demonstrated to be necessary at endogenous chromatin domains. This is thought to be due to the fact that most endogenous H3K27me3 domains contain many PREs, and individual PREs may be redundant. We show here that PREs near the wing selector gene vestigial have distinctive roles at their endogenous locus, even though both PREs are repressors in transgenes. First, a PRE near the promoter is required for vestigial activation and not for repression. Second, only the distal PRE contributes to H3K27me3, but even removal of both PREs does not eliminate H3K27me3 across the vestigial domain. Thus, endogenous chromatin domains appear to be intrinsically marked by H3K27me3, and PREs can enhance this chromatin modification at inactive genes.

2019-05-01 | GSE121028 | GEO

Multi-scale 3D genome rewiring during mouse neural development

Project description:Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We mapped comprehensively 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating topological domain (TAD) boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact stronger. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between proneural transcription factors appear in vivo. Finally, cell-type specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.

2017-10-18 | GSE96107 | GEO

Chromatin structure changes upon oxidative stress or UV irradiation in the yeast Saccharomyces cerevisiae

Project description:Development of molecular approaches based on chromosome conformation capture (3C) technology such as Hi-C, combined with methods for modeling and interpreting chromatin interaction data, have revolutionized the analysis of chromosome folding. Even if the impact of chromatin structure on gene expression seems likely, little is known about the dynamics of DNA compaction and the factors involved in this process still have to be determined. Using the yeast Saccharomyces cerevisiae as a model, we used Hi-C technology to evaluate how 3D chromatin structure changes during different cellular processes such as adaptation in response to stress or DNA repair. We optimized the protocol from Belton, J.M et al (1) to produce our Hi-C libraries, one from control cells, one from cells after oxidative stress and one from cells after UV irradiation. Preliminary analysis suggests that in response to oxidative stress, chromosomes tend to make more contacts in trans and less contacts in cis compared to normal condition.

2020-12-20 | E-MTAB-5825 | biostudies-arrayexpress

Polycomb-Dependent Chromatin Looping Contributes to Gene Silencing during Drosophila Development

Project description:Interphase chromatin is organized into topologically associating domains (TADs). Within TADs, chromatin looping interactions are formed between DNA regulatory elements, but their functional importance for the establishment of the 3D genome organization and gene regulation during development is unclear. Using high-resolution Hi-C experiments, we analyze higher order 3D chromatin organization during Drosophila embryogenesis and identify active and repressive chromatin loops that are established with different kinetics and depend on distinct factors: Zelda-dependent active loops are formed before the midblastula transition between transcribed genes over long distances. Repressive loops within polycomb domains are formed after the midblastula transition between polycomb response elements by the action of GAGA factor and polycomb proteins. Perturbation of PRE function by CRISPR/Cas9 genome engineering affects polycomb domain formation and destabilizes polycomb-mediated silencing. Preventing loop formation without removal of polycomb components also decreases silencing efficiency, suggesting that chromatin architecture can play instructive roles in gene regulation during development.

2018-06-08 | GSE103625 | GEO

Context dependent role of Pho binding sites in Polycomb complex recruitment in Drosophila

Project description:Polycomb group (PcG) proteins maintain the silenced state of key developmental genes, but how these proteins are recruited to specific regions of the genome is still not completely understood. In Drosophila, PcG proteins are recruited to Polycomb response elements (PREs) comprised of a flexible array of sites for sequence-specific DNA binding proteins, “PcG recruiters”, including Pho, Spps, Cg, GAF and many others. Pho is thought to play a central role in PcG recruitment. Early data showed that mutation of Pho binding sites in PREs in transgenes abrogated the ability of those PREs to repress gene expression. In contrast, genome-wide experiments in pho mutants or by Pho knockdown showed that PcG proteins can bind to PREs in the absence of Pho. Here we directly addressed the importance of Pho binding sites in two engrailed (en) PREs at the endogenous locus and in transgenes. Our results show that Pho binding sites are required for PRE activity in transgenes with a single PRE. In a transgene, two PREs together lead to stronger, more stable repression and confer some resistance to the loss of Pho binding sites. Making the same mutation in Pho binding sites has little effect on PcG-protein binding at the endogenous en gene. Overall, our data support the model that Pho is important for PcG binding but emphasize how multiple PREs and chromatin environment increase the ability of PREs to function in the absence of Pho.

2023-05-08 | GSE227553 | GEO

Robust Hi-C maps of enhancer-promoter interactions reveal the function of non-coding genome in neural development and diseases

Project description:Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input “easy Hi-C” protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.

2020-07-31 | GSE116825 | GEO

CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (Hi-C)

Project description:Spermatogenesis is a unidirectional differentiation process to produce haploid sperm. However, it remains largely unknown how the gene expression program is determined to direct a unidirectional differentiation. Here we unveil the high-resolution 3D chromatin architecture of male germ cells and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. At the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops specific to mitotic spermatogonia. On autosomes, CTCF-mediated 3D chromatin manifests the structural feature of meiosis-specific super-enhancer (meiotic SE) loci already in undifferentiated spermatogonia. In meiotic spermatocytes, the master transcription factor A-MYB is recruited to these meiotic SE loci to strengthen their 3D contacts to instruct the burst of meiotic gene expression. Further, SCML2 and A-MYB establish unique 3D chromatin of the sex chromosomes in meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin underlines epigenetic priming to direct unidirectional differentiation, thereby determining the cellular identity of the male germline.

2024-12-13 | GSE244676 | 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