Cargando…
Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements
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...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396287/ https://www.ncbi.nlm.nih.gov/pubmed/35996956 http://dx.doi.org/10.15252/msb.202110473 |
_version_ | 1784771897019334656 |
---|---|
author | Ibarra, Ignacio L Ratnu, Vikram S Gordillo, Lucia Hwang, In‐Young Mariani, Luca Weinand, Kathryn Hammarén, Henrik M Heck, Jennifer Bulyk, Martha L Savitski, Mikhail M Zaugg, Judith B Noh, Kyung‐Min |
author_facet | Ibarra, Ignacio L Ratnu, Vikram S Gordillo, Lucia Hwang, In‐Young Mariani, Luca Weinand, Kathryn Hammarén, Henrik M Heck, Jennifer Bulyk, Martha L Savitski, Mikhail M Zaugg, Judith B Noh, Kyung‐Min |
author_sort | Ibarra, Ignacio L |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9396287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93962872022-08-31 Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements Ibarra, Ignacio L Ratnu, Vikram S Gordillo, Lucia Hwang, In‐Young Mariani, Luca Weinand, Kathryn Hammarén, Henrik M Heck, Jennifer Bulyk, Martha L Savitski, Mikhail M Zaugg, Judith B Noh, Kyung‐Min Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2022-08-23 /pmc/articles/PMC9396287/ /pubmed/35996956 http://dx.doi.org/10.15252/msb.202110473 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Ibarra, Ignacio L Ratnu, Vikram S Gordillo, Lucia Hwang, In‐Young Mariani, Luca Weinand, Kathryn Hammarén, Henrik M Heck, Jennifer Bulyk, Martha L Savitski, Mikhail M Zaugg, Judith B Noh, Kyung‐Min Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title | Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title_full | Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title_fullStr | Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title_full_unstemmed | Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title_short | Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements |
title_sort | comparative chromatin accessibility upon bdnf stimulation delineates neuronal regulatory elements |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396287/ https://www.ncbi.nlm.nih.gov/pubmed/35996956 http://dx.doi.org/10.15252/msb.202110473 |
work_keys_str_mv | AT ibarraignaciol comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT ratnuvikrams comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT gordillolucia comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT hwanginyoung comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT marianiluca comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT weinandkathryn comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT hammarenhenrikm comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT heckjennifer comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT bulykmarthal comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT savitskimikhailm comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT zauggjudithb comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements AT nohkyungmin comparativechromatinaccessibilityuponbdnfstimulationdelineatesneuronalregulatoryelements |