Cohesin removal reprograms mitotic gene expression upon mitotic entry [RNA-seq I]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130558 | GEO | 2020/01/30
REPOSITORIES: GEO
Similar Datasets
Project description:During mitosis, the genome is restructured to facilitate chromosome segregation, accompanied by dramatic changes in gene expression. However, the mechanisms that underlie mitotic transcriptional regulation are unclear. In contrast to transcribed genes, centromere regions retain transcriptionally active RNA Polymerase II (RNAPII) in mitosis. Here, we demonstrate that chromosome-localized cohesin is necessary and sufficient to retain active RNAPII on mitotic centromeres. Failure to remove cohesin from mitotic chromosome arms dramatically alters mitotic gene expression, and results in a failure to release elongating RNAPII and nascent transcripts from mitotic chromosomes. We propose that prophase cohesin removal is the key step in reprogramming gene expression as cells transition from G2 to mitosis, and is temporally coupled with chromosome condensation to coordinate chromosome segregation with changes in gene expression.
2020-01-30 | GSE139846 | GEO
Project description:During mitosis, the genome is restructured to facilitate chromosome segregation, accompanied by dramatic changes in gene expression. However, the mechanisms that underlie mitotic transcriptional regulation are unclear. In contrast to transcribed genes, centromere regions retain transcriptionally active RNA Polymerase II (RNAPII) in mitosis. Here, we demonstrate that chromosome-localized cohesin is necessary and sufficient to retain active RNAPII on mitotic centromeres. Failure to remove cohesin from mitotic chromosome arms dramatically alters mitotic gene expression, and results in a failure to release elongating RNAPII and nascent transcripts from mitotic chromosomes. We propose that prophase cohesin removal is the key step in reprogramming gene expression as cells transition from G2 to mitosis, and is temporally coupled with chromosome condensation to coordinate chromosome segregation with changes in gene expression.
2020-01-30 | GSE139845 | GEO
Project description:By following chromatin occupancy of RNAPII and TOP1 using ChIP-seq throughout mitosis, we found that TOP1 is required for RNAPII translocation along genes. The stimulation of TOP1 activity through its interaction with RNAPII during elongation, allowed RNAPII clearance from genes in prometaphase and enabled proper chromosomal segregation. Interference with the TOP1-RNAPII interaction or acute depletion of TOP1 at the onset of mitosis impaired RNAPII spiking at promoters, which is necessary for the first pioneering round of transcription during mitotic exit, and triggered defects in the transcriptional program of the post-mitotic cells.
2021-11-11 | GSE171132 | GEO
Project description:The extreme length of chromosomal DNA requires organizing mechanisms to both promote functional genetic interactions and ensure faithful chromosome segregation when cells divide. Microscopy and genome wide contact frequency (Hi-C) analyses indicate that intra-chromosomal looping of DNA is a primary pathway of chromosomal organization during all stages of the cell cycle (Dekker, J. & Mirny, L. . Cell 164, 1110–1121 (2016). Although the enzymatic pathways required for DNA loop formation are yet to be fully characterized, the activity of the SMC family of proteins has been consistently associated with this process in interphase and mitosis. Here we use Hi-C to study the reorganization of budding yeast chromosome conformation in early mitosis and the role of SMCs in this process. Using polymer simulations, we find that the differences between interphase and mitotic Hi-C maps can be explained by the formation of intra-chromosomal (cis-) loops in mitotic chromosomes. We demonstrate that mitotic SMC cohesin activity is required for formation of cis-loops, independently of sister-chromatid cohesion. In contrast, SMC condensin is not required for loop formation in these early mitotic cells. Rather condensin activity promotes distinct higher order structures in the chromosomes at centromeres and in the rDNA proximal regions. Thus we demonstrate that cohesin-dependent cis-loops provide the primary higher order organization of budding yeast mitotic chromosomes, independently of condensin and sister chromatid cohesion.
2017-03-22 | GSE87311 | GEO
Project description:The fidelity of chromosome duplication through cell divisions requires timely binding and release of the cohesin. Cohesin is a ring-shaped protein complex linking newly replicated sister chromatids to ensure their appropriate transmission through mitosis. Upon commencement of mitosis cohesin is removed from DNA in two steps: first, from chromosome arms resulting in sister chromatid resolution, and, second, from centromers leading to sister chromatid segregation. As DNA of eukaryotic chromosomes is assembled into chromatin, regulation of sister chromatid cohesion-segregation may involve chromatin modifying machinery, but this link is not well understood. Here we report that H2A-H2B histone chaperone NAP1, a factor, which is primarily implicated in chromatin assembly, is required for cohesin release from mitotic chromosome arms. NAP1 and cohesin protein complex interact directly and share multiple binding sites on chromatin. Depletion of the NAP1 hinders cohesin removal during mitosis resulting in accumulation of unresolved sister chromatids. Thus, in addition to its well established functions in chromatin dynamics, histone chaperone NAP1 coordinates cell cycle dependent cohesin release. These results reveal a novel molecular pathway for sister chromatid resolution and emphasizes a role for histone chaperones in control of eukaryotic genome replication and transmission. Genome-wide NAP1 and Cohesin ChIP-chip profiling in Drosophila S2 cells. The supplementary bed file S2_cohesin_sites.bed contains cohesin binding sites obtained by intersecting the sets of significant ChIP-chip peaks for SA (a cohesin subunit; stromalin) and SMC1.
2012-07-25 | E-GEOD-30938 | biostudies-arrayexpress
Project description:FACT mediates cohesin function on chromatin 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.
2019-10-03 | PXD014896 | Pride
Project description:Chromatin fibres dynamically change their organisation during cell cycle. In interphase nucleus, chromatin fibres are evenly distributed whereas their spatial occupancy are reorganised to form condensed chromosomes in mitosis. This process called chromosome condensation is necessary for an accomplishment of faithful chromosome segregation. One of the Structural Maintenance of Chromosomes complexes, Condensin, is indispensable for chromosome condensation. It remains, however, unknown how Condensin plays its role in shaping mitotic chromosome. Here we show that chromatin fibres change their interacting partners; short-range contacts in interphase nucleus are converted into long-range interactions to shape condensed chromosomes. This conversion of interactions among chromatin fibres results in the formation of larger domains within mitotic chromosomes. Condensin is solely in charge of the conversion and large domain formation in fission yeast mitosis. Our results show how fission yeast Condensin is involved in shaping mitotic chromosomes.
2017-07-13 | GSE94475 | GEO
Project description:Chromatin fibres dynamically change their organisation during cell cycle. In interphase nucleus, chromatin fibres are evenly distributed whereas their spatial occupancy are reorganised to form condensed chromosomes in mitosis. This process called chromosome condensation is necessary for an accomplishment of faithful chromosome segregation. One of the Structural Maintenance of Chromosomes complexes, Condensin, is indispensable for chromosome condensation. It remains, however, unknown how Condensin plays its role in shaping mitotic chromosome. Here we show that chromatin fibres change their interacting partners; short-range contacts in interphase nucleus are converted into long-range interactions to shape condensed chromosomes. This conversion of interactions among chromatin fibres results in the formation of larger domains within mitotic chromosomes. Condensin is solely in charge of the conversion and large domain formation in fission yeast mitosis. Our results show how fission yeast Condensin is involved in shaping mitotic chromosomes.
2017-07-13 | GSE94474 | GEO
Project description:During mitosis, RNA polymerase and most transcription factors are excluded from the chromosomes and transcription ceases. The transcriptional re-activation of the genome, following mitosis, requires the re-setting of cell-type specific programs that were initially established during development. However, only about one-fifth of transcription factors are retained on chromosomes throughout mitosis and a subset of these have been shown to facilitate target gene reactivation during mitotic exit. How such M-bM-^@M-^\bookmarkingM-bM-^@M-^] factors bind to chromatin in mitosis and re-activate transcription is central to the stability of transcriptional programs across multiple cell cycles. We compared a diverse set of transcription factors involved in liver differentiation and found different modes of mitotic chromosome binding. The pioneer transcription factor FoxA1, which is among the first to bind liver genes in development, exhibits virtually complete mitotic chromosome binding, whereas other liver factors bind with a range of efficiencies. Yet genome-wide analysis shows that only about 15% of the FoxA1 interphase target sites are bound in mitosis; the latter include sites at genes for maintaining cell differentiation. FoxA1 mutants that perturb specific and nonspecific DNA binding reveal a significant contribution of nonspecific binding events in mitotic chromatin. Such nonspecific binding appears to spread from interphase FoxA1 targets and may serve as storage sites. The hierarchy of specific binding, nonspecific binding, partial chromatin binding, and failure to bind mitotic chromosomes reflects the temporal sequence of the factorsM-bM-^@M-^Y developmental roles in gene activation. Three replicate chIP-seq data sets each are included for mitotic and asynchronously cycling cells; a single input lane from each condition is also included.
2013-03-31 | E-GEOD-39241 | biostudies-arrayexpress
Project description:The fidelity of chromosome duplication through cell divisions requires timely binding and release of the cohesin. Cohesin is a ring-shaped protein complex linking newly replicated sister chromatids to ensure their appropriate transmission through mitosis. Upon commencement of mitosis cohesin is removed from DNA in two steps: first, from chromosome arms resulting in sister chromatid resolution, and, second, from centromers leading to sister chromatid segregation. As DNA of eukaryotic chromosomes is assembled into chromatin, regulation of sister chromatid cohesion-segregation may involve chromatin modifying machinery, but this link is not well understood. Here we report that H2A-H2B histone chaperone NAP1, a factor, which is primarily implicated in chromatin assembly, is required for cohesin release from mitotic chromosome arms. NAP1 and cohesin protein complex interact directly and share multiple binding sites on chromatin. Depletion of the NAP1 hinders cohesin removal during mitosis resulting in accumulation of unresolved sister chromatids. Thus, in addition to its well established functions in chromatin dynamics, histone chaperone NAP1 coordinates cell cycle dependent cohesin release. These results reveal a novel molecular pathway for sister chromatid resolution and emphasizes a role for histone chaperones in control of eukaryotic genome replication and transmission.
2012-07-26 | GSE30938 | GEO