Cohesin-dependence of neuronal gene expression relates to chromatin loop length
- Imperial College London, United Kingdom
- University of Bonn, Germany
- University of Pennsylvania, United States
- Rockefeller University, United States
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 remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the Immediate early gene Fos formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterised 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.
Data availability
RNAseq and 5C data generated in this study have been deposited at Gene Expression Omnibus under accession number GSE172429
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Cohesin-dependence of neuronal gene expression relates to chromatin loop lengthNCBI Gene Expression Omnibus, GSE172429.
Article and author information
Author details
Matthias Merkenschlager
Funding
Medical Research Council
- Matthias Merkenschlager
Wellcome Trust (099276/Z/12/Z)
- Matthias Merkenschlager
European Molecular Biology Organization (ALTF 1047-2012)
- Lesly Calderon
Human Frontiers in Science Program (LT00427/2013)
- Lesly Calderon
National Institutes of Health (1R01-MH120269)
- Jennifer E Phillips-Cremins
National Institutes of Health (1DP1OD031253)
- Jennifer E Phillips-Cremins
National Institutes of Health (1R01-NS114226)
- Jennifer E Phillips-Cremins
4D Nucleome Common Fund (1U01DK127405)
- Jennifer E Phillips-Cremins
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeremy J Day, University of Alabama at Birmingham, United States
Ethics
Animal experimentation: Laboratory bred mice of the appropriate genotype were maintained under SPF conditions and 12h light/dark cycle. Embryos were used to derive cells and tissues. Ethical approval was granted by the Home Office, UK, and the Imperial College London Animal Welfare and Ethical Review Body (AWERB).
Version history
- Preprint posted: February 24, 2021 (view preprint)
- Received: December 20, 2021
- Accepted: April 26, 2022
- Accepted Manuscript published: April 26, 2022 (version 1)
- Version of Record published: May 13, 2022 (version 2)
Copyright
© 2022, Calderon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cohesin-dependence of neuronal gene expression relates to chromatin loop length
eLife 11:e76539.
https://doi.org/10.7554/eLife.76539
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