stress-induced parp activation mediates recruitment of drosophila mi-2 to promote heat shock gene expression应激parp激活介导招聘果蝇米促进热休克基因的表达.pdfVIP

Stress-Induced PARP Activation Mediates Recruitment of Drosophila Mi-2 to Promote Heat Shock Gene Expression 1 2 3 2,4 Magdalena Murawska , Markus Hassler , Renate Renkawitz-Pohl , Andreas Ladurner , Alexander Brehm1* 1 Institute of Tumor Research and Molecular Biology, Philipps University, Marburg, Germany, 2 Genome Biology and Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany, 3 Developmental Biology, Philipps University, Marburg, Germany, 4 Department of Physiological Chemistry, Adolf- Butenandt-Institute, Ludwig-Maximilians University, Munich, Germany 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, s