Activator-Induced Spread of Poly(ADP-Ribose) Polymerase Promotes Nucleosome Loss at Hsp70

• Published in: Molecular cell 2012-01, Vol.45 (1), p.64-74
• Main Authors: Petesch, Steven J., Lis, John T.
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Heat-Shock Response; Histone Acetyltransferases - metabolism; Histone Deacetylases - metabolism; Histone Deacetylases - physiology; Histones - metabolism; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Nucleosomes - genetics; Nucleosomes - metabolism; Poly(ADP-ribose) Polymerases - metabolism; Poly(ADP-ribose) Polymerases - physiology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2011.11.015

Eukaryotic cells possess many transcriptionally regulated mechanisms to alleviate the nucleosome barrier. Dramatic changes to the chromatin structure of Drosophila melanogaster Hsp70 gene loci are dependent on the transcriptional activator, heat shock factor (HSF), and poly(ADP-ribose) polymerase (PARP). Here, we find that PARP is associated with the 5′ end of Hsp70, and its enzymatic activity is rapidly induced by heat shock. This activation causes PARP to redistribute throughout Hsp70 loci and Poly(ADP-ribose) to concurrently accumulate in the wake of PARP's spread. HSF is necessary for both the activation of PARP's enzymatic activity and its redistribution. Upon heat shock, HSF triggers these PARP activities mechanistically by directing Tip60 acetylation of histone H2A lysine 5 at the 5′ end of Hsp70, where inactive PARP resides before heat shock. This acetylation is critical for the activation and spread of PARP as well as for the rapid nucleosome loss over the Hsp70 loci. [Display omitted] ► PARP is rapidly activated and redistributed across Hsp70 following heat shock ► The activator of Hsp70, HSF, is necessary for PARP activation and redistribution ► HSF promotes Tip60 acetylation of H2AK5 upon heat shock at Hsp70 ► Tip60 is necessary for PARP activation and rapid nucleosome loss at Hsp70