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Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [ChIP-seq]

ABSTRACT: Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [ChIP-seq]

PROVIDER: PRJNA1041824 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26866647.fastq.gz	Fastqsanger.gz
	SRR26866648.fastq.gz	Fastqsanger.gz
	SRR26866649.fastq.gz	Fastqsanger.gz
	SRR26866650.fastq.gz	Fastqsanger.gz
	SRR26866651.fastq.gz	Fastqsanger.gz

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Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation

Project description:Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation

| PRJNA1041821 | ENA

Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [Micro-C]

Project description:Centromeres in budding yeast are surrounded by ~10-kb DNA loops generated by the cohesin complex. These peri-centromeric loops are shown to play a role in faithful chromosome segregation. It remains not fully understood how the dynamics of the peri-centromeric loops are controlled. Here we found that gene deletion of two cohesin regulators, Wpl1 and Eco1, resulted in larger peri-centromeric loops that connected the centromeres and genome regions up to ~ 300 kb distant in G2/M-arrested cells. Deletion of Wpl1 and Eco1 synergistically contributed to the loop size enlargement. ChIP-seq revealed that cohesin and its ATPase activator, Scc2, were colocalized at the anchor sites of the extended peri-centromeric loops, specifically in the double-deletion mutant Δwpl1 Δeco1. Consistently, acute depletion of Scc2 in the G2/M phase resulted in the disappearance of the extended loops. Given that Scc2 is bound prominently only at the centromeres in wild-type cells, our results suggest that Wpl1 and Eco1 jointly promote the dissociation of Scc2 from cohesin and inhibit excessive expansion of peri-centromeric DNA loop size. Notably, we found that nuclear division after benomyl block and release was significantly delayed in the Δwpl1 Δeco1 double-deletion mutant, and this delay was rescued by Scc2 depletion in the G2/M phase. This indicates that cohesin regulators cooperatively regulate the size of the peri-centromeric DNA loops to ensure faithful chromosome segregation.

2024-12-01 | GSE248143 | GEO

Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [ChIP-seq]

2024-12-01 | GSE248142 | GEO

Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [Micro-C]

Project description:Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation [Micro-C]

| PRJNA1041823 | ENA

Restriction mechanism of peri-centromeric DNA loop expansion necessary to ensure accurate chromosome segregation

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-01 | GSE248144 | GEO

Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation

Project description:Bub1 is required for the kinetochore/centromere localization of two essential mitotic kinases Plk1 and Aurora B. Surprisingly, stable depletion of Bub1 by ~95% in human cells marginally affects whole chromosome segregation fidelity. We show that CENP-U, which is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, is required to prevent chromosome mis-segregation in Bub1-depleted cells. Mechanistically, Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments, thereby ensuring accurate chromosome segregation. Furthermore, unlike its budding yeast homolog, the CENP-O complex does not regulate centromeric localization of Aurora B. Consistently, depletion of Bub1 or CENP-U sensitizes cells to the inhibition of Plk1 but not Aurora B kinase activity. Taken together, our findings provide mechanistic insight into the regulation of kinetochore function, which may have implications for targeted treatment of cancer cells with mutations perturbing kinetochore recruitment of Plk1 by Bub1 or the CENP-O complex.

2021-08-29 | GSE182827 | GEO

Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity

Project description:The chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error-correction of kinetochore-microtubule attachments and spindle assembly checkpoint. Correct spatiotemporal regulation of CPC localization is critical for its function. Phosphorylations of Histone H3 Thr3 and Histone H2A Thr120 and modification-independent nucleosome interactions involving Survivin and Borealin contribute to CPC centromere enrichment. However, mechanistic basis for how various nucleosome binding elements collectively contribute to CPC centromere enrichment and whether CPC has any non-catalytic role at centromere remain open questions. Combining a high-resolution cryoEM structure of CPC-bound H3Thr3ph nucleosome with atomic force microscopy and biochemical and cellular assays, we demonstrate that CPC employs multipartite interactions, which facilitate its engagement at nucleosome acidic patch and DNA entry-exit site. Perturbing the CPC-nucleosome interaction compromises protection against MNase digestion in vitro, as well as the centromere association of CPC and centromeric chromatin stability in cells. Our work suggests a non-catalytic role of CPC in maintaining centromeric chromatin features critical for kinetochore function.

2025-10-27 | PXD068775 | Pride

CENP-A associated lncRNAs influence chromosome segregation in human cells

Project description:Transcription occurs ubiquitously throughout non-coding parts of the genome, including at repetitive alpha-satellite DNA elements which comprise the majority of human centromeres. The function of temporally regulated centromeric transcription, and transcripts, is consequently a topic of intense investigation. In this study, we use high throughput approaches to identify and describe lncRNAs associated with the centromere specific histone variant CENP-A that arise from the transcription of specific centromeres at early G1, which we then show are physically associated with centromeres, and which are functionally necessary for accurate chromosome segregation. Targeted depletion of one such centromeric RNA, which originates from a single centromere, is sufficient to increase the frequency of chromosome segregation defects. These data support the emerging paradigm of the necessity of centromere-specific lncRNAs in the integrity of faithful chromosome segregation.

2019-11-26 | GSE137377 | GEO

Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation

Project description:Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation

| PRJNA758021 | ENA

Centromeric H2B monoubiquitination promotes noncoding transcription and chromatin integrity

Project description:Functional centromeres are essential for proper cell division. Centromeres are established largely by epigenetic processes resulting in incorporation of the histone H3 variant CENP-A. Here, we demonstrate the direct involvement of H2B monoubiquitination, mediated by RNF20 in humans or Brl1 in Schizosaccharomyces pombe, in centromeric chromatin maintenance. Monoubiquinated H2B (H2Bub1) is needed for this maintenance, promoting noncoding transcription, centromere integrity and accurate chromosomal segregation. A transient pulse of centromeric H2Bub1 leads to RNA polymerase II–mediated transcription of the centromere’s central domain, coupled to decreased H3 stability. H2Bub1-deficient cells have centromere cores that, despite their intact centromeric heterochromatin barriers, exhibit characteristics of heterochromatin, such as silencing histone modifications, reduced nucleosome turnover and reduced levels of transcription. In the H2Bub1-deficient cells, centromere functionality is hampered, thus resulting in unequal chromosome segregation. Therefore, centromeric H2Bub1 is essential for maintaining active centromeric chromatin.

2014-01-29 | GSE49874 | GEO

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