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CDK7 is Essential for Sustained Expression of the Condensin Complex, Chromatin Compaction, and Maintenance of Chromosomal Stability

ABSTRACT: CDK7 is Essential for Sustained Expression of the Condensin Complex, Chromatin Compaction, and Maintenance of Chromosomal Stability

PROVIDER: PRJNA673466 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR12955121.fastq.gz	Fastqsanger.gz
	SRR12955122_1.fastq.gz	Fastqsanger.gz
	SRR12955122_2.fastq.gz	Fastqsanger.gz
	SRR12955124_1.fastq.gz	Fastqsanger.gz

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CDK7 is Essential for Sustained Expression of the Condensin Complex, Chromatin Compaction, and Maintenance of Chromosomal Stability

Project description:Identifying a mechanism by which CDK7 inhibition promotes genomic stability in TNBC

2023-05-30 | GSE160534 | GEO

Condensin Accelerates Long-Range Intra-Chromosomal Interactions

Project description:The 3D genome organization plays a key role in regulating interactions among chromosomal loci. While Chromosome Conformation Capture (3C)-based methods have provided static snapshots of chromatin architecture, the kinetics of chromosomal encounters in live cells remain poorly characterized. In this study, we employ Chemically Induced Chromosomal Interaction (CICI) to measure encounter times between multiple loci pairs in G1-arrested budding yeast. Our results show that chromosome motion closely follows the Rouse polymer model, with similar diffusion parameters at all tested loci. Surprisingly, we find that long-range intra-chromosomal encounters occur significantly faster than inter-chromosomal encounters at similar 3D distances. Using targeted depletion experiments, we identify condensin, but not cohesin, as the complex responsible for these rapid intra-chromosomal interactions. This is further supported by Hi-C analysis, which reveals that condensin promotes long-distance intra-chromosomal interactions in G1 yeast. Through polymer simulations, we estimate that condensin extrudes chromatin at ~2 kb/s with a density of one complex per 1-2 Mb and a processivity of 120-220 kb. These findings uncover a novel role for condensin in shaping the interphase genome organization and provide new insights into chromosomal search dynamics in vivo.

2025-05-05 | GSE296183 | GEO

A role for condensin-mediator interaction in mitotic chromosomal organization [PRO-Seq]

Project description:Eukaryotic genomes are organized into layers of chromatin domains, such as topologically associating domains (TADs) and A/B compartments. TADs (i.e., cohesin-mediated chromatin domains) are restricted by CCCTC-binding factor (CTCF) and convergent genes in higher eukaryotes and fission yeast, respectively. However, molecular mechanisms underlying the formation of condensin-mediated chromatin domains remain largely unclear. Here, we investigate the role of newly identified interaction between the Cnd1 condensin and Pmc4 mediator subunits. We develop a condensin mutation, cnd1-K658E, that impairs the condensin-mediator interaction and find that this mutation diminishes condensin-mediated domains and causes defects in chromosomal segregation. The condensin-mediator interaction is involved in recruiting condensin to highly transcribed genes and mitotically activated genes, the latter of which demarcate condensin-mediated domains. Our study also predicted that the condensin-mediator interaction and its function in chromosomal segregation are potentially conserved in human cells. This study provides a novel insight into how genome-wide gene expression is connected to the mitotic chromosomal architecture via the condensin-mediator interaction.

2026-01-27 | GSE270577 | GEO

A role for condensin-mediator interaction in mitotic chromosomal organization [Hi-C]

2026-01-27 | GSE270576 | GEO

A role for condensin-mediator interaction in mitotic chromosomal organization [ChIP-Seq]

2026-01-27 | GSE270574 | GEO

Chromatin architecture is indirectly regulated by CDK7 transcriptional activity

Project description:Cyclin Dependent Kinase 7 (CDK7) is the core catalytic subunit of Cyclin Activating Kinase (CAK), a complex that has dual roles in cell cycle progression and transcription. While several CDK7 inhibitors are efficacious in preclinical models of cancer and have entered clinical trials, the mechanism(s) by which CDK7 promotes proliferation and cell viability is not well understood. Using triple negative breast cancer (TNBC) as a model, we found that inhibiting CDK7, either genomically or pharmacologically, induces mitotic dysfunction. Live and static cell imaging revealed that CDK7 inhibition prolongs mitosis and induces chromatin bridge formation, DNA double strand breaks, and abnormal nuclear features, all of which are indicative of mitotic catastrophe and chromosome instability. Transcriptome analyses revealed that CDK7 is essential for maintaining condensin complex gene expression, suggesting that CDK7 may sustain chromatin configuration, a role that extends beyond its impact on super-enhancers. Indeed, inhibiting CDK7 alters chromatin architecture consistent with condensin disruption. Confirming the importance of condensin regulation by CDK7, genetic suppression of a core subunit of this complex, structural maintenance of chromosome 2 (SMC2), phenocopies CDK7 inhibition. We report an undescribed role of CDK7 in maintaining chromatin structure and chromosome stability, as well as promoting proper mitoses, by sustaining condensin expression.

2023-05-30 | GSE223785 | GEO

Disruption of CDK7 signaling leads to catastrophic chromosomal instability coupled with a loss of condensin-mediated chromatin compaction.

Project description: Not available

| S-EPMC10300262 | biostudies-literature

Condensin Accelerates Long-Range Intra-Chromosomal Interactions

Project description:Condensin Accelerates Long-Range Intra-Chromosomal Interactions

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Molecular basis for condensin targeting to chromosomal loci [Hi-C]

Project description:Faithful chromosome segregation requires packaging of the genome on both global and local scales. Condensin plays a crucial role at pericentromeres to resist spindle forces and ensure the oriented attachment of kinetochores to microtubules at mitosis. Here we demonstrate that budding yeast condensin is recruited to pericentromeres through a direct interaction between its Ycg1 subunit and the pericentromeric adaptor protein, shugoshin (Sgo1). We identify a Short Linear Motif (SLiM), termed CR1, within the C-terminal region of Sgo1 which inserts into a conserved pocket on Ycg1. Disruption of this interface abolishes the Sgo1-condensin interaction, prevents condensin recruitment to pericentromeres and results in defective sister kinetochore biorientation in mitosis. Similar motifs to CR1 are found in known and potential condensin binding partners and the Ycg1 binding pocket is broadly conserved, including in mammalian CAP-G proteins. Overall, we uncover the molecular mechanism that targets condensin to define a specialized chromosomal domain.

2025-02-12 | GSE269442 | GEO

ARID1A regulates condensin II distribution and chromosomal partition

Project description:ARID1A regulates condensin II distribution and chromosomal partition

| PRJNA491495 | ENA