Abstract
Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme involved in DNA repair, chromatin remodeling and gene expression. PARP1 interactions with chromatin architectural multi-protein complexes (i.e. nucleosomes) alter chromatin structure resulting in changes in gene expression. Chromatin structure impacts gene regulatory processes including transcription, splicing, DNA repair, replication and recombination. It is important to delineate whether PARP1 randomly associates with nucleosomes or is present at specific nucleosome regions throughout the cell genome. We performed genome-wide association studies in breast cancer cell lines to address these questions. Our studies show that PARP1 associates with epigenetic regulatory elements genome-wide, such as active his-tone marks, CTCF and DNase hypersensitive sites. Additionally, the binding of PARP1 to chromatin genome-wide is mutually exclusive with DNA methylation pattern suggesting a functional interplay between PARP1 and DNA methylation. Indeed, inhibition of PARylation results in genome-wide changes in DNA methylation patterns. Our results suggest that PARP1 controls the fidelity of gene transcription and marks actively transcribed gene regions by selectively binding to transcriptionally active chromatin. These studies provide a platform for developing our understanding of PARP1's role in gene regulation.
| Original language | English |
|---|---|
| Article number | e0135410 |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 25 2015 |
Bibliographical note
Funding Information:We thank the Northwestern University Genomic Core for nucleosome ChIP-sequencing; Hong Quach of the Vincent J. Coates Genomics Sequencing Laboratory at the University of California Berkeley for the Infinium DNA methylation studies. The authors thank Professor Louis Hersh, the members of the Fondufe-Mittendorf Laboratory and Shaun Njovens for their support and critical reading of the manuscript. This research was supported by NIH grants P20GM103436 (ECR); 2P20 RR020171, 1R01ES024478, NSF 1517986 and IRSF grant (YNF-M).
Publisher Copyright:
© 2015 Nalabothula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Agricultural and Biological Sciences (all)
- General
