PARP-1 marks mitotic chromatin and regulates post-mitotic transcription. Niraj Lodhi, Alexei Tulin. Epigenetics and Progenitor Cells Program, Fox Chase Cancer Center, Philadelphia, PA.

   PARP-1 is an abundant nuclear protein that transfers poly(ADP)ribose residues to proteins in order to regulate DNA damage repair, chromatin remodeling and transcription. We found PARP-1 remain bound to chromatin through mitosis. However, it is not known whether its stable binding to mitotic chromatin can act as an epigenetic mark to maintain the re-establishment of gene expression state as cells exit mitosis. To explore this question, we performed ChIP-Seq to determine PARP-1 binding sites in asynchronous and mitotic cells. Additionally, we analyzed the localization of PARP-1 in these cells by confocal microscopy. ChIP-Seq data indicate that PARP-1 binds to different genes during mitosis, but we found evidence for a subset of genes bound to PARP-1 in both interphase and mitosis. Confocal data show there is a remarkable re-localization of PARP-1 in mitotic cells and it remains with chromatin during mitosis whereas other transcription factors disappear. Further, PARP-1 preferentially binds to the transcriptional start sites of genes, in both asynchronous and mitotic chromatin. Finally, we checked the transcription of genes after mitosis in PARP-1 knockdown cells or in presence of PARP-1 inhibitor. Results suggest transcription reduced by two fold in knockdown and partially reduced in PARP-1 inhibited cells. Overall results indicate that functional interaction and presence of PARP-1 in chromatin is required to re-establish post-mitotic transcription.