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) |
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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 (B), Haesler, Valérie, Surbek, Daniel, Müller, Martin (A) |
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: |
29 Mar 2023 23:38 |
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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