Nicotinamide dinucleotide modulates DNA methylation and gene transcription
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Poly (ADP-Riboysl) Polymerase 1 (PARP1) is a versatile protein that plays a key role in directing epigenetic pathways in cells by using nicotinamide adenine dinucleotide (NAD) as a substrate. We demonstrate that PARP1-directed adenine diphosphate (ADP) ribosylation impairs DNA Methyltransferase 1 (DNMT1) enzymatic activity by an NAD-promoted mechanism. This leads to demethylation of DNA, and thus reactivation of the CCAAT/enhancer-binding protein alpha (CEBPA) gene, suggesting the presence of a previously unknown NAD-modulated region within the locus. As an important tumor suppressor gene, epigenetic reactivation of CEPBA suggests possible therapeutic treatments for diseases associated with CEPBA suppression, such as many cancers.