STAG2 promotes the myelination transcriptional program in oligodendrocytes

Ningyan Cheng, Guanchen Li, Mohammed Kanchwala, Bret M. Evers, Chao Xing, Hongtao Yu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournaleLife
Volume11
DOIs
StatePublished - Aug 12 2022

Keywords

  • cell biology
  • chromosomes
  • cohesin
  • gene expression
  • loop extrusion
  • mouse
  • oligodendrocytes
  • transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'STAG2 promotes the myelination transcriptional program in oligodendrocytes'. Together they form a unique fingerprint.

Cite this