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Abstract

APOBEC2 is a member of the activation induced cytidine deaminase/apolipoprotein B editing complex (AID/APOBEC) family of nucleic acid deaminases. Even though it has the conserved zinc-dependent deaminase domain, it neither has an established cytidine deaminase activity nor a known nucleic acid ligand. However, APOBEC2 knockout models show defects in skeletal muscle, where APOBEC2 is highly expressed. Interestingly, none of these observations have been attributed to APOBEC2 acting directly on nucleic acids. In this work, I established that APOBEC2 is necessary for myotube differentiation. I showed that APOBEC2 is enriched within the nuclei of these myotubes, where it occupies the regulatory regions of genes related to cell differentiation processes. Moreover, the knockdown of APOBEC2 caused changes in gene expression of its target occupied genes. I then established that APOBEC2 directly interacts with the transcriptional corepressor histone deacetylase 1 (HDAC1), providing a potential mechanism for the observed gene expression changes. Furthermore, I demonstrated that APOBEC2 interacts directly with a single-stranded DNA ligand with an affinity comparable to other APOBEC ligand interactions. Given the evidence that APOBEC2 regulates transcription during myotube differentiation, interacts with the corepressor HDAC1, and binds DNA, I proposed that APOBEC2 is a transcriptional regulator.