TY - JOUR AU - Spinelli, Marialuigia AU - Boucard, Celiné AU - Ornaghi, Sara AU - Schoeberlein, Andreina AU - Irene, Keller AU - Coman, Daniel AU - Hyder, Fahmeed AU - Zhang, Longbo AU - Haesler, Valérie AU - Bordey, Angelique AU - Barnea, Eytan AU - Paidas, Michael AU - Surbek, Daniel AU - Mueller, Martin T1 - Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2 PY - 2021/10/22/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.132335 VL - 6 IS - 20 UR - https://doi.org/10.1172/jci.insight.132335 PB - The American Society for Clinical Investigation ER -