| First Author | Martinez-Zamudio R | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 13 | Pages | 2490-502 |
| PubMed ID | 22547677 | Mgi Jnum | J:186673 |
| Mgi Id | MGI:5432865 | Doi | 10.1128/MCB.06667-11 |
| Citation | Martinez-Zamudio R, et al. (2012) Histone ADP-ribosylation facilitates gene transcription by directly remodeling nucleosomes. Mol Cell Biol 32(13):2490-502 |
| abstractText | The packaging of DNA into nucleosomes imposes obstacles on gene transcription, and histone-modifying and nucleosome-remodeling complexes work in concert to alleviate these obstacles so as to facilitate transcription. Emerging evidence shows that chromatin-associated poly(ADP-ribose) polymerase 1 (PARP-1) and its enzymatic activity facilitate inflammatory gene transcription and modulate the inflammatory response in animal models. However, the molecular mechanisms by which PARP-1 enzymatic activity facilitates transcription are not well understood. Here we show that through an intracellular signaling pathway, lipopolysaccharide (LPS) stimulation induces PARP-1 enzymatic activity and the ADP-ribosylation of histones at transcriptionally active and accessible chromatin regions in macrophages. In vitro DNase I footprinting and restriction endonuclease accessibility assays reveal that histone ADP-ribosylation directly destabilizes histone-DNA interactions in the nucleosome and increases the site accessibility of the nucleosomal DNA to nucleases. Consistent with this, LPS stimulation-induced ADP-ribosylation at the nucleosome-occupied promoters of il-1beta, mip-2, and csf2 facilitates NF-kappaB recruitment and the transcription of these genes in macrophages. Therefore, our data suggest that PARP-1 enzymatic activity facilitates gene transcription through increasing promoter accessibility by histone ADP-ribosylation. |
