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

Gajendra Kumar Azad, Kenji Ito, Badi Sri Sailaja, Alva Biran, Malka Nissim-Rafinia, Yasuhiro Yamada, David T. Brown, Takumi Takizawa*, Eran Meshorer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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 KClinduced 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.

Original languageAmerican English
Pages (from-to)473-481
Number of pages9
JournalJournal of Cell Biology
Volume217
Issue number2
DOIs
StatePublished - 1 Feb 2018

Bibliographical note

Publisher Copyright:
© 2018 Azad et al.

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