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Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation (Hi-ChIP)

ABSTRACT: Transcriptional reprogramming during cell fate determination involves precise targeting of enhancers to tissue-specific genes. Enhancer-promoter interactions are regulated by different types of 3D chromatin organization, including compartmental domains and CTCF loops. To understand the contribution of these different levels of chromatin organization in cell lineage commitment, we analyzed changes in 3D organization during the differentiation of human embryonic stem cells (hESCs) into pancreatic islet organoids. We find that major events in chromatin reorganization, including decompaction of transposon-enriched heterochromatin, breakdown of poised enhancer-promoter interaction networks, gain or loss of CTCF loops and establishment of novel enhancer-promoter contacts, occur either sequentially or simultaneously. Transcriptionally activated transposons released from unstable heterochromatin compartments recruit CTCF to form new loops. In contrast, when released from poised long-range interaction networks, enhancers and genes crucial for cell differentiation recruit tissue-specific transcription factors by either direct binding or indirect 3D contacts containing RNA Polymerase II. Activation of stage-specific genes correlates with gain of CTCF binding at anchors of extended CTCF loops, suggesting changes in loop extrusion capacity. In agreement with this, we find a global increase in cohesin loading leading to longer residency on extended CTCF loops encompassing tissue-specific genes. Our findings provide new insights into how distinct types of chromatin organization affect the reprogramming of gene expression patterns to regulate cell lineage commitment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210525 | GEO | 2023/09/19

REPOSITORIES: GEO

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Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation

Project description:Transcriptional reprogramming during cell fate determination involves precise targeting of enhancers to tissue-specific genes. Enhancer-promoter interactions are regulated by different types of 3D chromatin organization, including compartmental domains and CTCF loops. To understand the contribution of these different levels of chromatin organization in cell lineage commitment, we analyzed changes in 3D organization during the differentiation of human embryonic stem cells (hESCs) into pancreatic islet organoids. We find that major events in chromatin reorganization, including decompaction of transposon-enriched heterochromatin, breakdown of poised enhancer-promoter interaction networks, gain or loss of CTCF loops and establishment of novel enhancer-promoter contacts, occur either sequentially or simultaneously. Transcriptionally activated transposons released from unstable heterochromatin compartments recruit CTCF to form new loops. In contrast, when released from poised long-range interaction networks, enhancers and genes crucial for cell differentiation recruit tissue-specific transcription factors by either direct binding or indirect 3D contacts containing RNA Polymerase II. Activation of stage-specific genes correlates with gain of CTCF binding at anchors of extended CTCF loops, suggesting changes in loop extrusion capacity. In agreement with this, we find a global increase in cohesin loading leading to longer residency on extended CTCF loops encompassing tissue-specific genes. Our findings provide new insights into how distinct types of chromatin organization affect the reprogramming of gene expression patterns to regulate cell lineage commitment.

2023-09-19 | GSE211101 | GEO

Regulation of cohesin loop extrusion underlies changes in enhancer-promoter interactions during pancreatic cell differentiation (Hi-C)

2023-09-19 | GSE210524 | GEO

CTCF binding polarity determines chromatin looping [4C]

Project description:CCCTC-binding factor (CTCF) is an architectural protein involved in the three-dimensional organization of chromatin. In this study, we systematically assayed the 3D genomic contact profiles of hundreds of CTCF binding sites in multiple tissues with high-resolution 4C-seq. We find both developmentally stable and dynamic chromatin loops. As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. To directly test this, we used CRISPR-Cas9 genome editing to delete core CTCF binding sites in three loci, including the CTCF site in the Sox2 super-enhancer. In all instances, CTCF and cohesin recruitment were lost, and chromatin loops with distal CTCF sites were disrupted or destabilized. Re-insertion of oppositely oriented CTCF recognition sequences restored CTCF and cohesin recruitment, but did not re-establish chromatin loops. We conclude that CTCF binding polarity plays a functional role in the formation of higher order chromatin structure. 4C-seq was performed on a large number of viewpoints in E14 embryonic stem cells, neural precursor cells and primary fetal liver cells

2015-10-29 | E-GEOD-72539 | biostudies-arrayexpress

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3D regulatory landscape of human naive pluripotency [ChIP-Seq]

Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. ChIP-seq data from naive and primed human embroynic stem cells.

2015-11-22 | E-GEOD-69646 | biostudies-arrayexpress

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Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. Polyadenylated RNA-seq from naive and primed human embroynic stem cells.

2015-11-22 | E-GEOD-69692 | biostudies-arrayexpress

3D regulatory landscape of human naive pluripotency [ChIAPET]

Project description:The control of cell identity is orchestrated by transcriptional and chromatin regulators in the context of specific chromosome structures. With the recent isolation of human naive embryonic stem cells (ESCs) representative of the ground state of pluripotency, it is possible to deduce this regulatory landscape in one of the earliest stages of human development. Here we generate cohesin ChIA-PET chromatin interaction data in naive and primed human ESCs and use it to reconstruct and compare the 3D regulatory landscapes of these two stages of early human development. The results reveal shared and stage-specific regulatory landscapes of topological domains and their subdomains, which consist of CTCF-CTCF/cohesin loops and enhancer-promoter/cohesin loops. The enhancer-promoter loop data reveal that genes with key roles in pluripotency are nearly always regulated by one or more super-enhancers, and show that these genes tend to occur in insulated neighborhoods. Our results reveal the key features of the 3D regulatory landscape of early human cells that form the foundation for embryonic development. ChIA_PET data against SMC1 from naive and primed human embroynic stem cells.

2015-11-22 | E-GEOD-69643 | biostudies-arrayexpress

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

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