PARP1-dependent eviction of the linker histone H1 mediates immediate early gene expression during neuronal activation
PARP1-dependent eviction of the linker histone H1 mediates immediate early gene expression during neuronal activation
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DOI：
10.1083/jcb.201703141
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发表时间：
2018-02-01
影响因子：
7.8
通讯作者：
Meshorer, Eran
中科院分区：
文献类型：
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作者：
Azad, Gajendra Kumar;Ito, Kenji;Meshorer, Eran
神经元刺激通过钙依赖性机制导致立即早期基因（IEG）表达。近年来，人们对神经元刺激后的转录反应给予了相当大的关注，但对神经元激活后染色质动力学的变化却知之甚少。在这里，我们使用荧光恢复后的光漂白，生化分馏，染色质免疫沉淀显示，氯化钾诱导的去极化在原代培养的皮层神经元导致快速释放的连接器组蛋白H1从染色质，伴随IEG表达。H1释放受到PARP抑制、PARP 1缺失、不可PAR化的H1以及磷酸化抑制和不可磷酸化的H1的抑制，导致IEG表达受阻。此外，神经元刺激后，IEG启动子上的H1被PARP 1取代，PARP抑制阻断了这种相互结合反应。我们的研究结果表明，神经元的兴奋和染色质可塑性之间的关系，通过确定的作用，多聚腺苷二磷酸核糖基化和磷酸化的H1在调节H1染色质驱逐和IEG表达在刺激的神经元。
Neuronal stimulation leads to immediate early gene (IEG) expression through calcium-dependent mechanisms. In recent years, considerable attention has been devoted to the transcriptional responses after neuronal stimulation, but relatively little is known about the changes in chromatin dynamics that follow neuronal activation. Here, we use fluorescence recovery after photobleaching, biochemical fractionations, and chromatin immunoprecipitation to show that KCl-induced depolarization in primary cultured cortical neurons causes a rapid release of the linker histone H1 from chromatin, concomitant with IEG expression. H1 release is repressed by PARP inhibition, PARP1 deletion, a non-PARylatable H1, as well as phosphorylation inhibitions and a nonphosphorylatable H1, leading to hindered IEG expression. Further, H1 is replaced by PARP1 on IEG promoters after neuronal stimulation, and PARP inhibition blocks this reciprocal binding response. Our results demonstrate the relationship between neuronal excitation and chromatin plasticity by identifying the roles of polyadenosine diphosphate ribosylation and phosphorylation of H1 in regulating H1 chromatin eviction and IEG expression in stimulated neurons.