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Publication : PARP1-dependent eviction of the linker histone H1 mediates immediate early gene expression during neuronal activation.

First Author  Azad GK Year  2018
Journal  J Cell Biol Volume  217
Issue  2 Pages  473-481
PubMed ID  29284668 Mgi Jnum  J:258234
Mgi Id  MGI:6116365 Doi  10.1083/jcb.201703141
Citation  Azad GK, et al. (2018) PARP1-dependent eviction of the linker histone H1 mediates immediate early gene expression during neuronal activation. J Cell Biol 217(2):473-481
abstractText  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.
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