title: Nucleosomal core histones mediate dynamic regulation of poly(ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity.
abstract: Poly(ADP-ribose) polymerase 1 protein (PARP1) mediates chromatin loosening and activates the transcription of inducible genes, but the mechanism of PARP1 regulation in chromatin is poorly understood. We have found that PARP1 interaction with chromatin is dynamic and that PARP1 is exchanged continuously between chromatin and nucleoplasm, as well as between chromatin domains. Specifically, the PARP1 protein preferentially interacts with nucleosomal particles, and although the nucleosomal linker DNA is not necessary for this interaction, we have shown that the core histones, H3 and H4, are critical for PARP1 binding. We have also demonstrated that the histones H3 and H4 interact preferentially with the C-terminal portion of PARP1 protein and that the N-terminal domain of PARP1 negatively regulates these interactions. Finally, we have found that interaction with the N-terminal tail of the H4 histone triggers PARP1 enzymatic activity. Therefore, our data collectively suggests a model in which both the regulation of PARP1 protein binding to chromatin and the enzymatic activation of PARP1 protein depend on the dynamics of nucleosomal core histone mediation.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Pinnola
authors.forename: Natasha
authors.initials: N
authors.lastname: Naumova
authors.forename: Meera
authors.initials: M
authors.lastname: Shah
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tulin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism*