Activator-induced spread of poly(ADP-ribose) polymerase promotes nucleosome loss at Hsp70.

Activator-induced spread of poly(ADP-ribose) polymerase promotes nucleosome loss at Hsp70.
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DOI:
10.1016/j.molcel.2011.11.015
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发表时间:
2012-01-13
期刊:
影响因子:
16
通讯作者:
Lis, John T.
Lis, John T.
中科院分区:
生物学1区
文献类型:
--
作者:
Petesch, Steven J.;Lis, John T.

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真核细胞具有许多转录调节机制来缓解核小体屏障。黑腹果蝇Hsp 70基因座的染色质结构的显著变化依赖于转录激活因子、热休克因子(HSF)和聚(ADP-核糖)聚合酶(PARP)。在此,我们发现PARP与Hsp 70的5′端结合,并且其酶活性被热休克迅速诱导。这种激活导致PARP在整个Hsp 70位点重新分布,并且聚(ADP-核糖)在PARP扩散之后同时积累。HSF对于PARP的酶活性的激活和其再分布都是必需的。在热休克时,HSF通过指导组蛋白H2 A赖氨酸5在Hsp 70的5′端的Tip 60乙酰化而机制性地触发这些PARP活性,其中在热休克之前无活性的PARP驻留在Hsp 70的5′端。这种乙酰化对于PARP的活化和扩散以及Hsp 70基因座上的核小体快速丢失至关重要。
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.
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