Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CTCF depletion uncouples the role of enhancer-promoter interactions and higher-order chromatin hubs in gene regulation during cellular differentiation [Tri-C]

ABSTRACT: Enhancers and promoters interact in 3D chromatin structures to regulate gene expression. The mechanisms that drive the formation of these structures and their function during cellular differentiation are incompletely understood. Here, we study the structure-function relationship of the genome in a lymphoid-to-myeloid differentiation system at very high resolution. We demonstrate a close correlation between binding of regulatory proteins, formation of chromatin interactions, and gene expression. By integrating analysis of single-allele topologies and computational modeling, we show that tissue-specific gene loci are organized into chromatin hubs, characterized by cooperative interactions between multiple enhancers, promoters, and CTCF-binding sites. Depletion of CTCF leads to a near-complete loss of these structures, which indicates that CTCF-mediated interactions provide a scaffold for chromatin hub formation. In contrast, the effects of CTCF depletion on gene expression are relatively mild and can be explained by rewired enhancer-promoter interactions. Together, our results demonstrate an instructive role for enhancer-promoter interactions in gene regulation during cellular differentiation, which does not depend on cooperative interactions in chromatin hubs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263640 | GEO | 2025/03/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CTCF depletion uncouples the role of enhancer-promoter interactions and higher-order chromatin hubs in gene regulation during cellular differentiation [ChIPmentation]

Project description:Enhancers and promoters interact in 3D chromatin structures to regulate gene expression. The mechanisms that drive the formation of these structures and their function during cellular differentiation are incompletely understood. Here, we study the structure-function relationship of the genome in a lymphoid-to-myeloid differentiation system at very high resolution. We demonstrate a close correlation between binding of regulatory proteins, formation of chromatin interactions, and gene expression. By integrating analysis of single-allele topologies and computational modeling, we show that tissue-specific gene loci are organized into chromatin hubs, characterized by cooperative interactions between multiple enhancers, promoters, and CTCF-binding sites. Depletion of CTCF leads to a near-complete loss of these structures, which indicates that CTCF-mediated interactions provide a scaffold for chromatin hub formation. In contrast, the effects of CTCF depletion on gene expression are relatively mild and can be explained by rewired enhancer-promoter interactions. Together, our results demonstrate an instructive role for enhancer-promoter interactions in gene regulation during cellular differentiation, which does not depend on cooperative interactions in chromatin hubs.

2025-03-03 | GSE263637 | GEO

CTCF depletion uncouples the role of enhancer-promoter interactions and higher-order chromatin hubs in gene regulation during cellular differentiation [RNA-seq]

2025-03-03 | GSE263639 | GEO

CTCF depletion uncouples the role of enhancer-promoter interactions and higher-order chromatin hubs in gene regulation during cellular differentiation [Capture-C]

2025-03-03 | GSE263636 | GEO

CTCF depletion uncouples the role of enhancer-promoter interactions and higher-order chromatin hubs in gene regulation during cellular differentiation [Micro-Capture-C]

2025-03-03 | GSE263638 | GEO

TCC in pluripotent and differentiated cells

Project description:Regulation of gene expression underlies the establishment and maintenance of cell identity. Chromatin structure and gene activity are linked. Recently CTCF anchored loops have been described as major features of chromatin organisation. However, the dynamics and role for these structures in differentiation is unknown. We used Tethered Chromatin Conformation Capture (TCC) to assess for the dynamics of CTCF-anchor loop formation upon differentiation of mouse embryonic stem cells (ESC) and neural stem cells (NSC).

2018-11-08 | E-MTAB-4870 | biostudies-arrayexpress

SRF is a new player in 3D genome organization and stem cell pluripotency

Project description:Serum response factor (SRF) is a transcription factor essential for cell proliferation, differentiation, and migration, and is required for primitive streak and mesoderm formation in the embryo. The canonical roles of SRF are mediated by a diverse set of context-dependent cofactors. Here we show that SRF physically interacts with CTCF and cohesin subunits at TAD boundaries and loop anchors. SRF reinforces the insulation of TADs and promotes the formation of long-range chromatin loops. In ES cells, SRF associates with Oct4, Sox2, and Nanog and contributes to the formation of 3D pluripotency hubs. Our findings reveal new roles of SRF in higher-order chromatin organization.

2024-10-14 | PXD049365 | Pride

Exploring the interaction between the SWI/SNF chromatin remodeling complex and the zinc finger factor CTCF

Project description:The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships between many CTCF-mediated activities involve direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases and BRG1 further support the interplay between master regulators of mammalian genome folding. Here we report a comprehensive LC-MS/MS mapping of the components of the SWI/SNF chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4-8 of CTCF, thus suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin-remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.

2021-09-09 | PXD022037 | Pride

CTCF binding in B cells and Plasmablasts

Project description:The mammalian CCCTC-binding factor (CTCF) regulates gene expression through the formation of higher order chromatin structures. Recent evidence has implicated a role for CTCF in regulating gene expression in the human MHCII locus. To investigate the role of CTCF in murine MHCII gene expression we mapped CTCF binding sites in B cells (MHCII+ cells) and Plasmablasts which are differentiated B cells that have silenced MHCII gene expression. These observations lead to the identification of differential CTCF binding during differentiation in these cell types and suggest mechanims of MHCII gene regulation. Comparison of CTCF binding in B cells and Plasmablasts in mice using ChIP-seq

2014-02-05 | E-GEOD-44637 | biostudies-arrayexpress

Acute depletion of CTCF rewires genome-wide chromatin accessibility

Project description:The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription. Here we systematically integrated multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, CRISPR-Cas9 survival dropout screening, time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewired genome-wide chromatin accessibility. Increased accessible chromatin regions were largely located adjacent to CTCF-binding sites at promoter regions and insulator sites and were associated with enhanced transcription of nearby genes. In addition, we used CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners in regulating downstream gene expression. We successfully identified 40 candidates, including multiple established partners (i.e., MYC) supported by all layers of evidence. Interestingly, many CTCF co-regulators (e.g., YY1, ZBTB7A) that have evident alterations of respective downstream gene expression do not show changes at their expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription. This study highlights CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation

2021-07-04 | PXD026484 | Pride

Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Hi-C]

Project description:The genome is organized into self-interacting chromatin domains containing genes and the cis-regulatory elements controlling their expression. How these domains form and how elements within them interact is unknown. We have developed Tri-C, a sensitive, high-resolution Chromosome Conformation Capture (3C) approach to identify concurrent chromatin interactions in single cells. Combining Tri-C with conventional 3C and polymer modeling, we show that, rather than folding into stable pre-formed loops, self-interacting domains form dynamic compartmentalized chromatin structures, delimited by CTCF/Cohesin boundaries. Within these tissue-specific domains, all regions of chromatin contact each other, but preferential structures are formed in which multiple enhancers and promoters interact simultaneously. Flanking CTCF/Cohesin-bound elements are excluded from these interactions and form distinct structures. These observations are best explained by a dynamic loop extrusion mechanism and subsequent stabilization of enhancer-promoter interactions, rather than the current view of long-range interactions occurring via the formation of discrete pre-formed chromatin loops.

2018-08-17 | GSE107939 | 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