AI Article Synopsis

  • Cohesin and CTCF are important for 3D genome organization and play a significant role in gene expression during neuronal maturation and maintenance.
  • In a study of mouse primary cortical neurons, cohesin was found to be essential for the expression of certain secondary response genes that rely on long-range chromatin interactions, while immediate early genes could be induced without it.
  • The dependence on cohesin for gene expression varied with the length of chromatin loops, highlighting its critical role in regulating genes involved in synaptic transmission and neurotransmitter signaling as neurons mature.

Article Abstract

Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent role for cohesin in the expression of genes that facilitate neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in mouse primary cortical neurons. Immediate early genes (IEGs) remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the IEGs formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterized by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend on cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106336PMC
http://dx.doi.org/10.7554/eLife.76539DOI Listing

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