Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptomere construction, 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 CNSmyelination 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.
[1]Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Expt Hematol, Cincinnati, OH 45229 USA.
[2]Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Cancer Biol & Dev Biol, Cincinnati, OH 45229 USA.
[3]Univ Texas SouthWestern Med Ctr, Integrat Biol Grad Training Program, Dallas, TX 75390 USA.
[4]Childrens Hosp Fudan Univ, Key Lab Birth Defects, Shanghai 201102, Peoples R China.
[5]Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
[6]Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Zhejiang Prov Key Lab Anti Canc Drug Res, Hangzhou 310058, Peoples R China.
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