Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2.

Spinelli, Marialuigia; Boucard, Céline; Ornaghi, Sara; Schoeberlein, Andreina; Keller, Irene; Coman, Daniel; Hyder, Fahmeed; Zhang, Longbo; Haesler, Valérie; Bordey, Angelique; Barnea, Eytan; Paidas, Michael; Surbek, Daniel; Mueller, Martin (2021). Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2. JCI insight, 6(20) JCI Insight 10.1172/jci.insight.132335

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin

UniBE Contributor:

Spinelli, Marialuigia; Boucard, Céline; Schoeberlein, Andreina; Keller, Irene; Haesler, Valérie; Surbek, Daniel and Müller, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2379-3708

Publisher:

JCI Insight

Language:

English

Submitter:

Monika Zehr

Date Deposited:

27 Dec 2021 14:50

Last Modified:

27 Dec 2021 14:54

Publisher DOI:

10.1172/jci.insight.132335

PubMed ID:

34676826

Uncontrolled Keywords:

Drug therapy Neurodevelopment Neuroscience Therapeutics

BORIS DOI:

10.48350/163049

URI:

https://boris.unibe.ch/id/eprint/163049

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