Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selective compartmentalization in condensin-depleted mitotic chromosomes

ABSTRACT: During the G2/M transition, SMC protein complexes including extrusive-cohesin, cohesive-cohesin and condensin are co-present on the chromatin. Yet, the precise pattern of interactions among these complexes and the subsequent impact on chromatin architecture remain elusive. Here, we utilize mitotic chromosome as a unified experimental platform to dissect their rules of engagement. We find that condensin disrupts the focal binding of both extrusive- and cohesive-cohesin, leading to disassembly of TADs and loops. Reciprocally, both extrusive- and cohesive-cohesin affect condensin activity and mitotic chromosome organization. Extrusive-cohesin impairs chromosome helicity and cohesive-cohesin reduces helical layer size. In the absence of condensin, extrusive-cohesin establishes TADs and loops. Conversely, cohesive-cohesin by itself does not induce these structures, nor does it form independent peaks, suggesting lack of extruding activity. Instead, cohesive-cohesin modulates pre-existing TADs and loops, intensifying intra-TAD interactions while restricting loop expansion. Collectively, our data reveal a tripartite interplay among extrusive-cohesin, cohesive-coheisn and condensin that dynamically sculpts chromatin architecture during mitotic progression

ORGANISM(S): Mus musculus

PROVIDER: GSE269952 | GEO | 2024/12/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RB is a cell cycle-regulated repressor of cohesin-dependent loop formation

Project description:Chromatin organization and cell cycle are tightly intertwined in eukaryotes, but the underlying mechanisms remain unclear. We investigated how the retinoblastoma protein (RB), a key cell cycle regulator, influences chromatin architecture. Chromosome conformation capture assays reveal that RB loss increases the number and size of cohesin-dependent loops and strengthens topologically associating domains (TADs). RB shows extensive colocalization with cohesin in the human genome, and it impacts cohesin’s distribution on chromatin. Active RB evicted cohesin from RB-bound TAD boundaries, repressed insulator activity, and enhanced the expression of non-E2F target genes that are important for cell adhesion. We conclude that RB has a central role in the interplay between cell cycle and chromatin organization. This role safeguards chromatin architecture and controls transcription.

2024-11-01 | E-MTAB-13566 | biostudies-arrayexpress

Wapl-mediated release of Scc1-cohesin regulates chromosome structure and segregation in mouse oocytes

Project description:Cohesin is essential for genome folding and chromosome inheritance through cell divisions. In somatic cells, both of these functions are mediated by Scc1-cohesin, which in mitosis is released from chromosomes by Wapl and separase. In mammalian oocytes, cohesion is mediated by Rec8-cohesin. Scc1 is also expressed but neither required nor sufficient for cohesion, and its function in oocytes is unknown. Likewise, it is unknown whether Wapl regulates one or both cohesin complexes and chromosome segregation in mature oocytes. Using conditional mouse mutagenesis, we show that in meiosis I Wapl is required for proper chromosome segregation, predominantly releases Scc1-cohesin from chromosomes and promotes production of euploid eggs. Using single-nucleus Hi-C, we found that Scc1 is essential for chromatin loops and topologically associating domains (TADs) in oocytes. Increasing Scc1 residence time on chromosomes by Wapl depletion leads to vermicelli formation and intra-loop structures but, unlike in mitotic cells, does not increase loop size. This implies that loop size has reached a maximum in oocytes, possibly because it is limited by barriers such as cohesive cohesin. We conclude that distinct cohesin complexes generate loops and cohesion in mammalian oocytes and propose that the same principle applies to all cell types and species.

2020-03-04 | GSE132264 | GEO

Cohesin-dependent compaction of mitotic chromosomes in budding yeast

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

3D topology of the SMC2/SMC4 sub-complex from chicken condensin I revealed by cross-linking and molecular modelling

Project description:SMC proteins are essential components of three protein complexes that are important for chromosome structure and function. The cohesin complex holds replicated sister chromatids together, whereas the condensin complex has an essential role in mitotic chromosome architecture. Both are involved in interphase genome organisation. SMC-containing complexes are large (>650 kDa for condensin) and contain long anti-parallel coiled-coils. They are thus difficult subjects for conventional crystallographic and electron cryomicroscopic studies. Here we have used amino acid-selective cross-linking and mass spectrometry (CLMS) combined with structure prediction to develop a full-length molecular draft 3D-structure of the SMC2/SMC4 dimeric backbone of chicken condensin. We assembled homology-based molecular models of the globular heads and hinges with the lengthy coiled-coils modelled in fragments, using numerous high-confidence cross-links and accounting for potential irregularity. Our experiments reveal that isolated condensin complexes can exist with their coiled-coil segments closely apposed to one another along their lengths and define the relative spatial alignment of the two anti-parallel coils. The centres of the coiled-coils can also approach one another closely in situ in mitotic chromosomes. In addition to revealing structural information, our cross-linking data suggest that both H2A and H4 may have roles in condensin interactions with chromatin.

2015-07-13 | PXD001835 | Pride

Condensin association with chromosomes depends on a DNA binding domain formed by its HEAT-repeat subunits

Project description:Condensin protein complexes play central roles in the three-dimensional organization of chromosomes during mitotic and meiotic cell divisions. How condensin interacts with its chromatin substrates to promote sister chromatid decatenation and segregation is largely unknown. Previous work suggested that condensin, in addition to encircling chromatin fibers topologically within the large ring-shaped structure formed by its structural maintenance of chromosomes (SMC) and kleisin subunits, contacts DNA directly. Here we describe the discovery of a binding domain for double-stranded DNA helices formed by condensinM-bM-^@M-^Ys HEAT-repeat subunits. Using detailed mapping data of the interfaces between the HEAT-repeat and the kleisin subunits, we generated mutant complexes that lack the Ycg1/CAP-G HEAT-repeat subunit. These tetrameric condensin complexes fail to associate stably with chromosomes in yeast and human cells. We suggest that condensin controls chromosome architecture by stabilizing chromatin loops of chromatin fibers through interaction with its unconventional HEAT-repeat DNA binding domain. Analysis of condensin binding genomewide in a wild type and a condensin mutant

2014-05-16 | E-GEOD-55948 | biostudies-arrayexpress

Absolute quantification of cohesin and its regulators in human cells

Project description:The organisation of mammalian genomes into loops and topologically associated domains (TADs) regulates gene expression. The formation and maintenance of loops and TADs depends on the protein complex cohesin, which also holds replicated sister chromatids together from S phase until mitosis. To understand how cohesin functions, it is essential to know how many cohesin complexes and regulators exist in a typical cell and how they are distributed genome-wide. Here, we have used quantitative mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching to measure the absolute number and dynamics of core subunits and regulators of the cohesin complex in human cells. We find that 60000 – 134000 cohesin complexes are bound to chromatin per G1 HeLa cell, suggesting that cohesin most likely does not occupy all its binding sites concurrently. We incorporate our data into mathematical models and discuss implications for how cohesin might contribute to genome organisation and sister chromatid cohesion.

2019-11-13 | PXD012712 | Pride

RNA Pol II transcription antagonises mitotic chromosome assembly and segregation by condensin

Project description:Condensin drives mitotic chromosome assembly by folding chromatin into loops and is enriched in the vicinity of highly expressed genes, but the significance of such proximity with respect to condensin activity has remained unclear. Here, by modulating the occupancy of RNA Pol II in vivo, we show that transcription plays no role in the steady state association of condensin with DNA. Rather, transcription stalls and even displaces condensin, hindering its ability to fold chromatin and to support chromosome segregation. Our results highlight a key aspect of the integrated functioning of condensin and suggest that a tight control of transcription underlies mitotic chromosome assembly.

2024-02-03 | GSE236395 | GEO

Bacillus subtilis SMC complexes juxtapose chromosome arms as they travel from origin to terminus

Project description:Structural maintenance of chromosomes (SMC) complexes play critical roles in chromosome dynamics in virtually all organisms but how they function remains poorly understood. In Bacillus subtilis, SMC condensin complexes are topologically loaded at centromeric sites adjacent to the replication origin. Here we provide evidence that these ring-shaped assemblies tether the left and right chromosome arms together while traveling from the origin to the terminus (>2 Mb) at rates >50kb/min. Condensin movement scales linearly with time arguing for an active transport mechanism. These data support a model in which SMC complexes function by processively enlarging DNA loops. Loop formation followed by processive enlargement provides a mechanism for how condensin complexes compact and resolve sister chromatids in mitosis and how cohesin generates topologically associating domains (TADs) during interphase.

2017-02-03 | GSE85612 | GEO

Condensin I folds the C. elegans genome [Hi-C]

Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.

2024-04-18 | GSE199721 | GEO

Condensin I folds the C. elegans genome [Ribo-Zero-seq]

2024-04-18 | GSE199719 | GEO