title: Kinase-mediated changes in nucleosome conformation trigger chromatin decondensation via poly(ADP-ribosyl)ation.
abstract: Dynamically controlled posttranslational modifications of nucleosomal histones alter chromatin condensation to regulate transcriptional activation. We report that a nuclear tandem kinase, JIL-1, controls gene expression by activating poly(ADP-ribose) polymerase-1 (PARP-1). JIL-1 phosphorylates the C terminus of the H2Av histone variant, which stimulates PARP-1 enzymatic activity in the surrounding chromatin, leading to further modification of histones and chromatin loosening. The H2Av nucleosome has a higher surface representation of PARP-1 binding patch, consisting of H3 and H4 epitopes. Phosphorylation of H2Av by JIL-1 restructures this surface patch, leading to activation of PARP-1. Exposure of Val61 and Leu23 of the H4 histone is critical for PARP-1 binding on nucleosome and PARP-1 activation following H2Av phosphorylation. We propose that chromatin loosening and associated initiation of gene expression is activated by phosphorylation of H2Av in a nucleosome positioned in promoter regions of PARP-1-dependent genes.
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors: Colin J
authors: CJ
authors: Thomas
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors: Elena
authors: E
authors: Kotova
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors: Mark
authors: M
authors: Andrake
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors: Jared
authors: J
authors: Adolf-Bryfogle
authors: Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors: Robert
authors: R
authors: Glaser
authors: Adolf Butenandt Institute, Ludwig Maximilian University, Schillerstrasse 44, 80336 Munich, Germany.
authors: Catherine
authors: C
authors: Regnard
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. Electronic address: alexei.tulin@fccc.edu.
authors: Alexei V
authors: AV
authors: Tulin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D006657:Histones / Q000737:chemistry*; D007150:Immunohistochemistry; D008836:Micrococcal Nuclease / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D009707:Nucleosomes / Q000737:chemistry*; D016366:Open Reading Frames; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D000939:Epitopes; D006657:Histones; D009707:Nucleosomes; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; C524850:Parp protein, Drosophila; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C507306:JIL-1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D008836:Micrococcal Nuclease