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

• Type of Material: Article
• Authors: Jordi Fernandez-Albert, Universidad Miguel Hernández; Michal Lipinski, Universidad Miguel Hernández; Maria T. Lopez-Cascales, Universidad Miguel Hernández; M. Jordan Rowley, Emory University; Ana M. Martin-Gonzalez, Universidad Miguel Hernández; Beatriz del Blanco, Universidad Miguel Hernández; Victor Corces, Emory University; Angel Barco, Universidad Miguel Hernández
• Language: English
• Date: 2019-10-01
• Publisher: NATURE PORTFOLIO
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41593-019-0476-2
• Title of Journal or Parent Work: NATURE NEUROSCIENCE
• Volume: 22
• Issue: 10
• Start Page: 1718
• End Page: +
• Grant/Funding Information: JF-A and MTL-C are recipients of fellowships from the Spanish Ministry of Science and Innovation (MICINN). AB research is supported by grants SAF2017–87928-R and SEV-2017–0723 from MICINN co-financed by ERDF, PROM ETEO/2016/026 from the Generalitat Valenciana, and RGP0039/2017 from the Human Frontiers Science Program Organization (HFSPO). MJR is supported by the NIH Pathway to Independence Award K99/R00 GM127671.VGC research is supported by the U.S. Public Health Service Award (R01) GM035463 from the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”.
• Keywords: ACTIVITY-INDUCED TRANSCRIPTION; GENOME; GENE-EXPRESSION; MECHANISMS; HISTONE ACETYLATION; Neurosciences; PLASTICITY; Science & Technology; READ ALIGNMENT; IDENTIFICATION; Neurosciences & Neurology; REVEALS; Life Sciences & Biomedicine; CHROMATIN

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.