STAG2 promotes the myelination transcriptional programin oligodendrocytes
- The University of Texas Southwestern Medical Center, United States
- Westlake University, China
Abstract
Cohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer-promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate cohesin consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. To probe the physiological functions of cohesin, we created conditional knockout (cKO) mice with Stag2 deleted in the nervous system. Stag2 cKO mice exhibit growth retardation, neurological defects, and premature death, in part due to insufficient myelination of nerve fibers. Stag2 cKO oligodendrocytes exhibit delayed maturation and downregulation of myelination-related genes. Stag2 loss reduces promoter-anchored loops at downregulated genes in oligodendrocytes. Thus, STAG2-cohesin generates promoter-anchored loops at myelination-promoting genes to facilitate their transcription. Our study implicates defective myelination as a contributing factor to cohesinopathy and establishes oligodendrocytes as a relevant cell type to explore the mechanisms by which cohesin regulates transcription.
Data availability
The RNA-seq, scRNA-seq, ChIP-seq, and Hi-C datasets generated and analyzed during the current study are available in the GEO repository, with the accession number GSE186894.
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STAG2 promotes the myelination transcriptional program in oligodendrocytesNCBI Gene Expression Omnibus, GSE186894.
Article and author information
Author details
Funding
National Natural Science Foundation of China (Project 32130053)
- Hongtao Yu
National Institutes of Health (1R01GM124096)
- Hongtao Yu
Cancer Prevention and Research Institute of Texas (RP160667-P2)
- Hongtao Yu
Welch Foundation (I-1441)
- Hongtao Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animals were handled in accordance with institutional guidelines of the Institutional Animal Care and Use Committee (IACUC; AAALAC unit number 000673) of University of Texas (UT) Southwestern Medical Center under the animal protocol number (APN) 102335.
Copyright
© 2022, Cheng 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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