lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS

Danyang He, Jincheng Wang, Yulan Lu, Yaqi Deng, Chuntao Zhao, Lingli Xu, Yinhuai Chen, Yueh Chiang Hu, Wenhao Zhou, Q. Richard Lu

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination. Overexpression of lncOL1 promotes precocious oligodendrocyte differentiation in the developing brain, whereas genetic inactivation of lncOL1 causes defects in CNS myelination and remyelination following injury. Functional analyses illustrate that lncOL1 interacts with Suz12, a component of polycomb repressive complex 2, to promote oligodendrocyte maturation, in part, through Suz12-mediated repression of a differentiation inhibitory network that maintains the precursor state. Together, our findings reveal a key lncRNA epigenetic circuitry through interaction with chromatin-modifying complexes in control of CNS myelination and myelin repair.

Original languageEnglish (US)
Pages (from-to)362-378
Number of pages17
JournalNeuron
Volume93
Issue number2
DOIs
StatePublished - Jan 18 2017

Keywords

  • chromatin remodeling
  • EZH2
  • functional genomics
  • long noncoding RNA
  • myelination
  • neural precursors
  • oligodendrocyte differentiation
  • OPC
  • polycomb repressive complex
  • remyelination

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    He, D., Wang, J., Lu, Y., Deng, Y., Zhao, C., Xu, L., Chen, Y., Hu, Y. C., Zhou, W., & Lu, Q. R. (2017). lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS. Neuron, 93(2), 362-378. https://doi.org/10.1016/j.neuron.2016.11.044