Integrative PARP1 and ADP-ribosylation profiling in cells undergoing oncogene-gene-induced senescence Raw sequence reads. Homo sapiens

Cellular senescence is a cell fate triggered in response to a variety of non-lethal stressors acting as a safeguard of damaged or dysfunctional cells. In line with its prominent role in aging and age-related diseases, the elimination of senescent cells holds excellent therapeutic promise.PARP1 (Poly (ADP-ribose) polymerase 1) is an abundant nuclear protein that catalyzes the transfer of ADP-ribose (ADPr) from NAD+. PARP1 function is associated with DNA damage repair, transcriptional regulation of inflammatory genes, and other prominent chromatin structural and regulatory roles.We display independent enzymatic and nucleosome binding functions of PARP1 in senescence-associated gene regulation. PARP-mediated ADP-ribosylation of chromatin is significantly enriched at active enhancers of lowly expressed genes where it recruits context-dependent TFs to fine-tune transcription and chromatin accessibility. PARP1 nucleosome binding is crucial at promoters, where it acts to maintain positioning and subsequently regulates transcription.