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RNAPII and DNA supercoiling regulate cohesin engagement in neurons [ChIP-Seq]

ABSTRACT: Chromatin looping by CTCF and cohesin is thought to be crucial for chromosome organization and gene transcription. Yet the precise relationships between CTCF, cohesin, and transcription in neurons are still poorly understood. To address this issue, we compared the occupancy of CTCF and the cohesin subunit, SMC1, relative to transcriptionally engaged RNAPII and as a function of stimulus-dependent transcription in cultured mouse cortical neurons. We show that CTCF and cohesin are enriched at transcription start sites (TSS) and that their levels increase with the level of transcriptionally engaged RNAPII, suggesting that RNAPII facilitates the engagement of CTCF and cohesin. Unexpectedly, while neuronal stimulation causes widespread transcriptional activation, it resulted in the rapid genome-wide loss of SMC1 signals, including at the TSS of genes, loop anchors, and TAD boundaries. Activity-dependent reductions in cohesin were independent of CTCF but were mimicked by inhibiting topoisomerase IIb (TOP2B), which resolves torsional stress from DNA supercoiling. We show that neuronal stimulation elevates DNA supercoiling and that increasing torsional stress triggers the dissociation of SMC1 from chromatin. Overall, these results suggest that modulation of torsional stress could be a physiologically relevant mechanism of regulating cohesin engagement and chromatin architecture in neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE282196 | GEO | 2025/11/01

REPOSITORIES: GEO

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RNAPII and DNA supercoiling regulate cohesin engagement in neurons [RNA-Seq]

Project description:Chromatin looping by CTCF and cohesin is thought to be crucial for chromosome organization and gene transcription. Yet the precise relationships between CTCF, cohesin, and transcription in neurons are still poorly understood. To address this issue, we compared the occupancy of CTCF and the cohesin subunit, SMC1, relative to transcriptionally engaged RNAPII and as a function of stimulus-dependent transcription in cultured mouse cortical neurons. We show that CTCF and cohesin are enriched at transcription start sites (TSS) and that their levels increase with the level of transcriptionally engaged RNAPII, suggesting that RNAPII facilitates the engagement of CTCF and cohesin. Unexpectedly, while neuronal stimulation causes widespread transcriptional activation, it resulted in the rapid genome-wide loss of SMC1 signals, including at the TSS of genes, loop anchors, and TAD boundaries. Activity-dependent reductions in cohesin were independent of CTCF but were mimicked by inhibiting topoisomerase IIb (TOP2B), which resolves torsional stress from DNA supercoiling. We show that neuronal stimulation elevates DNA supercoiling and that increasing torsional stress triggers the dissociation of SMC1 from chromatin. Overall, these results suggest that modulation of torsional stress could be a physiologically relevant mechanism of regulating cohesin engagement and chromatin architecture in neurons.

2025-11-01 | GSE282195 | GEO

RNAPII and DNA supercoiling regulate cohesin engagement in neurons [RNA-Seq]

Project description:RNAPII and DNA supercoiling regulate cohesin engagement in neurons [RNA-Seq]

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Architectural protein subclasses shape 3-D organization of genomes during lineage commitment

Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. Analysis of higher-order chromatin chromatin architecture in mouse ES cells and ES-derived NPCs. Analysis of CTCF and Smc1 occupied sites in ES-derived NPCs.

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The contribution of cohesin-SA1 to chromatin architecture and gene expression in two murine tissues [RNA-seq]

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