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Nat Neurosci. 2019 Oct;22(10):1718-1730. doi: 10.1038/s41593-019-0476-2. Epub 2019 Sep 9.

Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus.

Author information

1
Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Sant Joan d'Alacant, Alicante, Spain.
2
Department of Biology, Emory University, Atlanta, GA, USA.
3
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
4
Nencki Institute of Experimental Biology PAS, Warsaw, Poland.
5
Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Sant Joan d'Alacant, Alicante, Spain. abarco@umh.es.

Abstract

Activity-driven transcription plays an important role in many brain processes, including those underlying memory and epilepsy. Here we combine genetic tagging of nuclei and ribosomes with RNA sequencing, chromatin immunoprecipitation with sequencing, assay for transposase-accessible chromatin using sequencing and Hi-C to investigate transcriptional and chromatin changes occurring in mouse hippocampal excitatory neurons at different time points after synchronous activation during seizure and sparse activation by novel context exploration. The transcriptional burst is associated with an increase in chromatin accessibility of activity-regulated genes and enhancers, de novo binding of activity-regulated transcription factors, augmented promoter-enhancer interactions and the formation of gene loops that bring together the transcription start site and transcription termination site of induced genes and may sustain the fast reloading of RNA polymerase complexes. Some chromatin occupancy changes and interactions, particularly those driven by AP1, remain long after neuronal activation and could underlie the changes in neuronal responsiveness and circuit connectivity observed in these neuroplasticity paradigms, perhaps thereby contributing to metaplasticity in the adult brain.

PMID:
31501571
DOI:
10.1038/s41593-019-0476-2
[Indexed for MEDLINE]

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