TY  - JOUR
AU  - Lorenzo, Jose Paulo
AU  - Molla, Linda
AU  - Amro, Elias M. E.
AU  - Ibarra, Ignacio L
AU  - Ruf, Sandra
AU  - Neber, Cedrik
AU  - Gkougkousis, Christos
AU  - Ridani, Jana
AU  - Subramani, Poorani Ganesh
AU  - Boulais, Jonathan
AU  - Harjanto, Dewi
AU  - Vonica, Alin
AU  - Di Noia, Javier M
AU  - Dieterich, Christoph
AU  - Zaugg, Judith B
AU  - Papavasiliou, Fotini
TI  - APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 121
IS  - 17
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DKFZ-2024-00816
SP  - e2312330121
PY  - 2024
N1  - #EA:D150#LA:D150#
AB  - 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.
KW  - Chromatin: genetics
KW  - Muscle Proteins: metabolism
KW  - APOBEC Deaminases: genetics
KW  - Cytidine Deaminase: metabolism
KW  - Muscle Fibers, Skeletal: metabolism
KW  - Cell Differentiation: genetics
KW  - RNA, Messenger: genetics
KW  - Myoblasts: metabolism
KW  - DNA
KW  - APOBEC-1 Deaminase: genetics
KW  - APOBEC family (Other)
KW  - DNA binding (Other)
KW  - muscle differentiation (Other)
KW  - safeguard factor (Other)
KW  - transcriptional regulator (Other)
KW  - Chromatin (NLM Chemicals)
KW  - Muscle Proteins (NLM Chemicals)
KW  - APOBEC Deaminases (NLM Chemicals)
KW  - Cytidine Deaminase (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - DNA (NLM Chemicals)
KW  - APOBEC-1 Deaminase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38625936
DO  - DOI:10.1073/pnas.2312330121
UR  - https://inrepo02.dkfz.de/record/289494
ER  -