JCI Insight (Oct 2021)

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

  • Marialuigia Spinelli,
  • Celiné Boucard,
  • Sara Ornaghi,
  • Andreina Schoeberlein,
  • Keller Irene,
  • Daniel Coman,
  • Fahmeed Hyder,
  • Longbo Zhang,
  • Valérie Haesler,
  • Angelique Bordey,
  • Eytan Barnea,
  • Michael Paidas,
  • Daniel Surbek,
  • Martin Mueller

Journal volume & issue
Vol. 6, no. 20

Abstract

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Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes’ fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned.

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