Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

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.

Automated summary

The H19/SAHH axis plays a significant role in diffuse white matter injury in premature infants, where sPIF and H19 regulate NCOR2 expression and impact oligodendrocyte differentiation markers. Therefore, during brain recovery, sPIF and H19 may assist in myelin protection and have potential therapeutic applications for neurodegenerative diseases.