title: Stress-induced PARP activation mediates recruitment of Drosophila Mi-2 to promote heat shock gene expression.
abstract: Eukaryotic cells respond to genomic and environmental stresses, such as DNA damage and heat shock (HS), with the synthesis of poly-[ADP-ribose] (PAR) at specific chromatin regions, such as DNA breaks or HS genes, by PAR polymerases (PARP). Little is known about the role of this modification during cellular stress responses. We show here that the nucleosome remodeler dMi-2 is recruited to active HS genes in a PARP-dependent manner. dMi-2 binds PAR suggesting that this physical interaction is important for recruitment. Indeed, a dMi-2 mutant unable to bind PAR does not localise to active HS loci in vivo. We have identified several dMi-2 regions which bind PAR independently in vitro, including the chromodomains and regions near the N-terminus containing motifs rich in K and R residues. Moreover, upon HS gene activation, dMi-2 associates with nascent HS gene transcripts, and its catalytic activity is required for efficient transcription and co-transcriptional RNA processing. RNA and PAR compete for dMi-2 binding in vitro, suggesting a two step process for dMi-2 association with active HS genes: initial recruitment to the locus via PAR interaction, followed by binding to nascent RNA transcripts. We suggest that stress-induced chromatin PARylation serves to rapidly attract factors that are required for an efficient and timely transcriptional response.
authors.affiliation: Institute of Tumor Research and Molecular Biology, Philipps University, Marburg, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Murawska
authors.forename: Markus
authors.initials: M
authors.lastname: Hassler
authors.forename: Renate
authors.initials: R
authors.lastname: Renkawitz-Pohl
authors.forename: Andreas
authors.initials: A
authors.lastname: Ladurner
authors.forename: Alexander
authors.initials: A
authors.lastname: Brehm
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; D029721:Drosophila Proteins; C116095:Mi-2 protein, Drosophila; D011064:Poly Adenosine Diphosphate Ribose; D012313:RNA; D011065:Poly(ADP-ribose) Polymerases; D000251:Adenosine Triphosphatases