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Lorenzo, J.P.* ; Molla, L.* ; Amro, E.M.* ; Ibarra Del Rio, I.A. ; Ruf, S.* ; Neber, C.* ; Gkougkousis, C.* ; Ridani, J.* ; Subramani, P.G.* ; Boulais, J.* ; Harjanto, D.* ; Vonica, A.* ; di Noia, J.M.* ; Dieterich, C.* ; Zaugg, J.B.* ; Papavasiliou, F.N.*

APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation.

Proc. Natl. Acad. Sci. U.S.A. 121:e2312330121 (2024)
DOI PMC
Creative Commons Lizenzvertrag
The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide (APOBEC) family is composed of nucleic acid editors with roles ranging from antibody diversification to RNA editing. APOBEC2, a member of this family with an evolutionarily conserved nucleic acid-binding cytidine deaminase domain, has neither an established substrate nor function. Using a cellular model of muscle differentiation where APOBEC2 is inducibly expressed, we confirmed that APOBEC2 does not have the attributed molecular functions of the APOBEC family, such as RNA editing, DNA demethylation, and DNA mutation. Instead, we found that during muscle differentiation APOBEC2 occupied a specific motif within promoter regions; its removal from those regions resulted in transcriptional changes. Mechanistically, these changes reflect the direct interaction of APOBEC2 with histone deacetylase (HDAC) transcriptional corepressor complexes. We also found that APOBEC2 could bind DNA directly, in a sequence-specific fashion, suggesting that it functions as a recruiter of HDAC to specific genes whose promoters it occupies. These genes are normally suppressed during muscle cell differentiation, and their suppression may contribute to the safeguarding of muscle cell fate. Altogether, our results reveal a unique role for APOBEC2 within the APOBEC family.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apobec Family ; Dna Binding ; Muscle Differentiation ; Safeguard Factor ; Transcriptional Regulator; Rna-editing Enzyme; Polypeptide 2 Apobec2; Phosphodiesterase 1a; Dna Demethylation; Muller Glia; Deaminase; Expression; Zebrafish; Proteins; Identity
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 121, Heft: 17, Seiten: , Artikelnummer: e2312330121 Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Helmholtz-Fonds (Helmholtz-Fonds e.V.)