4.8 Article

Activation-induced chromatin reorganization in neurons depends on HDAC1 activity

Journal

CELL REPORTS
Volume 38, Issue 7, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2022.110352

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Funding

  1. National Science Centre [UMO-2015/18/E/NZ3/00730, 2014/15/N/NZ2/00379, 2017/24/T/NZ2/00307, 2019/35/O/ST6/02484, 2014/14/M/NZ4/00561]
  2. Foundation for Polish Science TEAM-TECH Core Facility project NGS platform for comprehensive diagnostics and personalized ther-apy in neuro-oncology
  3. Foundation for Polish Science
  4. European Union under the European Regional Development Fund
  5. H2020-MSCA-COFUND-2014 grant Bio4-Med [665735]

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Spatial chromatin organization is crucial for transcriptional regulation in neurons and is influenced by activity-induced chromatin condensation, histone modifications, and rearrangements in chromosome territories and nuclear speckles. HDAC1 plays a key role in this process.
Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed in vitro in cultured rat hippocampal neurons as well as in vivo in the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons.

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