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Ibarra Del Rio, I.A. ; Ratnu, V.S.* ; Gordillo, L.* ; Hwang, I.Y.* ; Mariani, L.* ; Weinand, K.* ; Hammarén, H.M.* ; Heck, J.* ; Bulyk, M.L.* ; Savitski, M.M.* ; Zaugg, J.B.* ; Noh, K.M.*

Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements.

Mol. Syst. Biol. 18:e10473 (2022)
Verlagsversion Forschungsdaten Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Neuronal stimulation induced by the brain-derived neurotrophic factor (BDNF) triggers gene expression, which is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. However, its role in chromatin regulation is unclear. Here, using temporal profiling of chromatin accessibility and transcription in mouse primary cortical neurons upon either BDNF stimulation or depolarization (KCl), we identify features that define BDNF-specific chromatin-to-gene expression programs. Enhancer activation is an early event in the regulatory control of BDNF-treated neurons, where the bZIP motif-binding Fos protein pioneered chromatin opening and cooperated with co-regulatory transcription factors (Homeobox, EGRs, and CTCF) to induce transcription. Deleting cis-regulatory sequences affect BDNF-mediated Arc expression, a regulator of synaptic plasticity. BDNF-induced accessible regions are linked to preferential exon usage by neurodevelopmental disorder-related genes and the heritability of neuronal complex traits, which were validated in human iPSC-derived neurons. Thus, we provide a comprehensive view of BDNF-mediated genome regulatory features using comparative genomic approaches to dissect mammalian neuronal stimulation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Enhancers ; Gene Expression ; Neuronal Stimulation ; Post-mitotic Neurons ; Transcription Factors
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Zeitschrift Molecular Systems Biology
Quellenangaben Band: 18, Heft: 8, Seiten: , Artikelnummer: e10473 Supplement: ,
Verlag EMBO Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen NHGRI NIH HHS
Deutsche Forschungsgemeinschaft (DFG)