Cohesin depleted cells rebuild active and inactive nuclear compartments after mitosis
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ABSTRACT:
PROVIDER: PRJNA606036 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11067700_1.fastq.gz | Fastqsanger.gz | |||
| SRR11067700_2.fastq.gz | Fastqsanger.gz | |||
| SRR11067701_1.fastq.gz | Fastqsanger.gz | |||
| SRR11067701_2.fastq.gz | Fastqsanger.gz | |||
| SRR11067702_1.fastq.gz | Fastqsanger.gz |
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Project description:Nuclear functions are essentially linked to nuclear compartmentalization. This study demonstrates that cohesin rings as anchors of chromatin loops are dispensable to rebuild a functional nuclear compartmentalization in cohesin depleted cells after passing through mitosis and formation of one daughter cell with a multilobulated nucleus (MLN). Super-resolved microscopy reveals co-aligned active and inactive nuclear compartments (ANC/INC) in these postmitotic nuclei, likely corresponding to A and B compartments, detected with Hi-C. MLN carry chromosome territories, built from chromatin domain clusters, pervaded by a system of interchromatin channels harboring splicing speckles. Channels are lined by transcriptionally competent chromatin, whereas repressed chromatin with higher compaction locates in the interior of chromatin clusters. MLN pass through S-phase with typical early and mid-to-late replication patterns. Sites of DNA synthesis become physically larger, consistent with a model where cohesin dependent loop extrusion tends to compact intervals of replicating chromatin, whereas their genomic boundaries are associated with compartmentalization.
2020-10-05 | GSE145099 | GEO
Project description:Chromosome conformation capture approaches have shown that interphase chromatin is organized into an architectural framework of Mb-sized compartments and sub-Mb-sized topological domains. Cohesin controls chromosome topology to facilitate DNA repair and chromosome segregation in cycling cells, and also associates with active enhancers and promoters and with CTCF to form long-range interactions important for gene regulation. We find that architectural compartments - a major feature of interphase chromatin organization – are maintained in non-cycling mouse thymocytes after genetic depletion of cohesin in vivo. Cohesin was however required for specific long-range interactions within permissive (A-type) compartments, where cohesin-regulated genes reside. Cohesin depletion diminished interactions between cohesin-bound sites, while alternative interactions between chromatin features associated with transcriptional activation and repression became more prominent, with corresponding changes in gene expression. Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within pre-existing chromosomal compartments.
2013-08-13 | GSE48763 | GEO
Project description:Cohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is less well understood. Using live-cell and super-resolved 3D microscopy, here we find that cohesin depletion in a human colon cancer derived cell line results in endomitosis and a single multilobulated nucleus with chromosome territories pervaded by interchromatin channels. Chromosome territories contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. These clusters form microscopically defined, active and inactive compartments, which likely correspond to A/B compartments, which are detected with ensemble Hi-C. Splicing speckles are observed nearby within the lining channel system. We further observe that the multilobulated nuclei, despite continuous absence of cohesin, pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity.
| S-EPMC7708632 | biostudies-literature
Project description:In the mammalian nucleus, heterochromatin is segregated from transcriptionally active euchromatic regions (A compartments), forming large, condensed, and inactive nuclear compartments (B compartments). However, the mechanisms underlying its spatial organization remain incompletely understood. We previously demonstrated that simultaneous depletion of H3K9 methylation, H3K27me3, and H2A monoubiquitination in immortalized mouse embryonic fibroblasts (iMEFs) leads to heterochromatin weakening and alterations in nuclear compartments. However, the overall pattern of A/B compartments remains largely preserved even under these conditions, suggesting the involvement of unknown factors. Since histone deacetylation is a key factor in transcriptional repression, we investigated the impact of histone deacetylase (HDAC) inhibition on nuclear compartments by treating cells depleted of H3K9 methylation, H3K27me3, and H2A K119 monoubiquitylation (H2AK119ub/uH2A) with the HDAC inhibitor Trichostatin A (TSA). We performed Hi-C analysis to assess the nuclear compartment changes. Our results showed that, although TSA treatment globally increased H3K27ac levels, the difference in H3K27ac enrichment between A/B compartments remained evident, and nuclear compartments were minimally affected. These findings suggest that factors other than HDACs maintain nuclear compartmentalization when repressive chromatin modifications are depleted.
2025-04-30 | GSE294422 | GEO
Project description:In the mammalian nucleus, heterochromatin is segregated from transcriptionally active euchromatic regions (A compartments), forming large, condensed, and inactive nuclear compartments (B compartments). However, the mechanisms underlying its spatial organization remain incompletely understood. We previously demonstrated that simultaneous depletion of H3K9 methylation, H3K27me3, and H2A monoubiquitination in immortalized mouse embryonic fibroblasts (iMEFs) leads to heterochromatin weakening and alterations in nuclear compartments. However, the overall pattern of A/B compartments remains largely preserved even under these conditions, suggesting the involvement of unknown factors. Since histone deacetylation is a key factor in transcriptional repression, we investigated the impact of histone deacetylase (HDAC) inhibition on nuclear compartments by treating cells depleted of H3K9 methylation, H3K27me3, and H2A K119 monoubiquitylation (H2AK119ub/uH2A) with the HDAC inhibitor Trichostatin A (TSA). We performed Hi-C analysis to assess the nuclear compartment changes. Our results showed that, although TSA treatment globally increased H3K27ac levels, the difference in H3K27ac enrichment between A/B compartments remained evident, and nuclear compartments were minimally affected. These findings suggest that factors other than HDACs maintain nuclear compartmentalization when repressive chromatin modifications are depleted.
2025-04-30 | GSE294421 | GEO
Project description:Sister chromatid cohesion (SCC), the pairing of sister chromatids following DNA replication until mitosis, is established by loading of the cohesin complex on newly replicated chromatids. Cohesin must then be maintained until mitosis to prevent segregation defects and aneuploidy. However, how SCC is established and maintained until mitosis remains incompletely understood and emerging evidence suggests that replication stress may lead to premature SCC loss. Here, we report that the single-stranded DNA-binding protein CTC1-STN1-TEN1 (CST) aids in SCC. CST primarily functions in telomere length regulation but also has known roles in replication restart and DNA repair. Following depletion of CST subunits, we observed an increase in the complete loss of SCC. Additionally, we determined that CST associates with the cohesin complex. Unexpectedly, we did not find evidence of altered cohesion or mitotic progression in the absence of CST; however, we did find that treatment with various replication inhibitors increased the association between CST and cohesin. Since replication stress was recently shown to induce SCC loss, we hypothesized that CST may be required to maintain or remodel SCC following DNA replication fork stalling. In agreement with this idea, SCC loss was greatly increased in CST-depleted cells following exogenous replication stress. Based on our findings, we propose that CST aids in the maintenance of SCC at stalled replication forks to prevent premature cohesion loss.
2021-07-28 | PXD026264 | Pride
Project description:Cohesin is a key regulator of genome architecture with roles in sister chromatid cohesion and the organisation of higher-order structures during interphase and mitosis. The recruitment and mobility of cohesin complexes on DNA are restricted by nucleosomes. Here we show that cohesin role in chromosome organization requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin dependent compartmentalization of chromosomes into loop domains.
2019-10-11 | GSE118534 | GEO
Project description:We report genome wide mapping of the histone variant H2A.Z during G0/G1 and mitosis in T24 bladder cancer cells. The results show that the broad enrichment pattern of H2A.Z near transcription start sites of active genes is maintained during mitosis. Furthermore, using H2A.Z localization to visualize nucleosome positioning near the start site, we see that the +1 nucleosome of active genes shifts upstream to occupy the transcription start sites during mitosis and the nucleosome depleted region is shortened. H2A.Z is also maintained on the -2 nucleosome which also shifts towrds the transcription start site during mitosis, further contributing to the shorteneing of the nucleosome depleted region. Examination of H2A.Z duing G0/G1 and mitosis in bladder cancer cells
2010-06-24 | E-GEOD-19568 | biostudies-arrayexpress
Project description:Three-dimensional organization of mitotic chromosomes is established by cohesin and condensin complexes. In the centromere, cohesin maintains sister chromatid pairing until anaphase onset, while condensin provides elastic resistance to spindle forces. However, how condensin and cohesin structure vertebrate centromeres remains unclear. By super-resolution imaging, Capture-C analysis and polymer modeling we show that vertebrate centromeres are partitioned into two condensin-dependent subdomains during mitosis. This bipartite sub-structure is found in human, mouse and chicken centromeres, and is therefore a fundamental feature of vertebrate centromere. Super-resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores with each subdomain capable of binding a distinct microtubule bundle. Cohesin helps to link the centromere subdomains, limiting their separation in response to spindle forces and preventing merotelic attachments. The two-domain structure described here may have implications for avoiding chromosomal instability as uncoupling of centromere subdomains is a common feature of lagging chromosomes in cancer cells.
2024-04-01 | GSE254181 | GEO
Project description:Three-dimensional organization of mitotic chromosomes is established by cohesin and condensin complexes. In the centromere, cohesin maintains sister chromatid pairing until anaphase onset, while condensin provides elastic resistance to spindle forces. However, how condensin and cohesin structure vertebrate centromeres remains unclear. By super-resolution imaging, Capture-C analysis and polymer modeling we show that vertebrate centromeres are partitioned into two condensin-dependent subdomains during mitosis. This bipartite sub-structure is found in human, mouse and chicken centromeres, and is therefore a fundamental feature of vertebrate centromere. Super-resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores with each subdomain capable of binding a distinct microtubule bundle. Cohesin helps to link the centromere subdomains, limiting their separation in response to spindle forces and preventing merotelic attachments. The two-domain structure described here may have implications for avoiding chromosomal instability as uncoupling of centromere subdomains is a common feature of lagging chromosomes in cancer cells.
2024-04-01 | GSE254659 | GEO