The cohesin release factor WAPL restricts chromatin loop extension.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE95015 | GEO | 2017/05/03
SECONDARY ACCESSION(S): PRJNA375736
REPOSITORIES: GEO
Similar Datasets
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.
| S-EPMC5422210 | biostudies-literature
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The ring-shaped cohesin complex shapes the 3D genome by looping together convergent CTCF sites along chromosomes. We show here with high-resolution Hi-C analysis that chromatin loop size can be increased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL alsoincreased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL also prevents looping between incorrectly oriented CTCF sites. Through haploid genetics we find that WAPL deficiency bypasses the need for cohesin’s DNA loader SCC4 and we reveal that SCC4 promotes the extension of chromatin loops. We provide functional evidence in support of the model that chromatin loops are processively enlarged by the extrusion of DNA from cohesin rings. We conclude that the balanced activity of SCC4 and WAPL enables cohesin to correctly structure chromosomes to ensure proper transcriptional control.
2017-05-03 | GSE95521 | GEO
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The ring-shaped cohesin complex shapes the 3D genome by looping together convergent CTCF sites along chromosomes. We show here with high-resolution Hi-C analysis that chromatin loop size can be increased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL alsoincreased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL also prevents looping between incorrectly oriented CTCF sites. Through haploid genetics we find that WAPL deficiency bypasses the need for cohesin’s DNA loader SCC4 and we reveal that SCC4 promotes the extension of chromatin loops. We provide functional evidence in support of the model that chromatin loops are processively enlarged by the extrusion of DNA from cohesin rings. We conclude that the balanced activity of SCC4 and WAPL enables cohesin to correctly structure chromosomes to ensure proper transcriptional control.
2017-05-03 | GSE95520 | GEO
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The ring-shaped cohesin complex shapes the 3D genome by looping together convergent CTCF sites along chromosomes. We show here with high-resolution Hi-C analysis that chromatin loop size can be increased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL alsoincreased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL also prevents looping between incorrectly oriented CTCF sites. Through haploid genetics we find that WAPL deficiency bypasses the need for cohesin’s DNA loader SCC4 and we reveal that SCC4 promotes the extension of chromatin loops. We provide functional evidence in support of the model that chromatin loops are processively enlarged by the extrusion of DNA from cohesin rings. We conclude that the balanced activity of SCC4 and WAPL enables cohesin to correctly structure chromosomes to ensure proper transcriptional control.
2017-05-03 | GSE95518 | GEO
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.
2017-05-03 | GSE95014 | GEO
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.
2017-05-03 | GSE94993 | GEO
Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.
2017-05-03 | GSE94992 | GEO
Project description:The cohesin release factor WAPL restricts chromatin loop extension.
| PRJNA375736 | ENA
Project description:During mitotic prophase, cohesins are removed from chromosome arms by Wapl to ensure faithful sister chromatid separation. However, during female meiosis I, the resolution of chiasmata requires the proteolytic cleavage of cohesin subunit Rec8 along chromosome arms by Separase to separate homologs, and thus the role of Wapl remained unknown. Here, we report that Wapl functions as a regulator of spindle assembly checkpoint (SAC) to prevent aneuploidy in meiosis I. Depletion of Wapl accelerates meiotic progression, inactivates SAC, and causes meiotic defects such as aberrant spindle/chromosome structure and incorrect kinetochore-microtubule (K-MT) attachment, consequently leading to aneuploid eggs. Notably, we identify Bub3 as a binding partner of Wapl by immunoprecipitation and mass spectrometry analysis. We further determine that Wapl controls the SAC activity by maintaining Bub3 protein level and document that exogenous Bub3 restores the normal meiosis in Wapl-depleted oocytes. Together, our findings uncover unique, noncanonical roles for Wapl in mediating control of the SAC in female meiosis I.
| S-EPMC7141834 | biostudies-literature
Project description:Epstein-Barr virus (EBV) is a ubiquitous human pathogen that is etiologically linked to several cancers and has been connected to multiple sclerosis. EBV employs a series of latency programs, including latency III, latency II, and latency I, to persistently colonize the B-cell compartment. Each of these programs is associated with human malignancies. However, our understanding remains incomplete of how these distinct latency programs are epigenetically restricted. While regulation of the chromatin structure of the EBV genome by cohesin and CTCF contributes to genome regulation, the function of the cohesin release factor Wings Apart-Like Protein Homolog (WAPL) had not previously been understood. In this study, we employ RNA-seq combined with immunofluorescence analysis to determine that loss of WAPL leads to aberrant expression of the oncogenic latent membrane proteins LMP1 and LMP2A in latency I Burkitt lymphoma cells. Through a combination of Hi-C, Hi-ChIP, and ChIP-qPCR, we uncover that WAPL loss causes alterations in looping across the EBV genome and specifically induces formation of loops between the LMP promoter and the oriLyt enhancers. We propose that EBV coopts WAPL to maintain a strict latency I state and, without WAPL, leaky expression of the LMP proteins occurs.
2024-08-06 | GSE264502 | GEO