PuSH - Publication Server of Helmholtz Zentrum München

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)
Publ. Version/Full Text Research data Research data 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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Enhancers ; Gene Expression ; Neuronal Stimulation ; Post-mitotic Neurons ; Transcription Factors
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Journal Molecular Systems Biology
Quellenangaben Volume: 18, Issue: 8, Pages: , Article Number: e10473 Supplement: ,
Publisher EMBO Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants NHGRI NIH HHS
Deutsche Forschungsgemeinschaft (DFG)