Neuronal activity modifies the chromatin accessibility landscape in the adult brain.
Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation using an assay for transposase-accessible chromatin using sequencing (ATAC-seq). We found genome-wide changes 1 h after activation, with enrichment of gained-open sites at active enhancer regions and at binding sites for AP1-complex components, including c-Fos. Some changes remained stable for at least 24 h. Functional analysis further implicates a critical role of c-Fos in initiating, but not maintaining, neuronal activity-induced chromatin opening. Our results reveal dynamic changes of chromatin accessibility in adult mammalian brains and suggest an epigenetic mechanism by which transient neuronal activation leads to dynamic changes in gene expression via modifying chromatin accessibility.
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yijing
Y
Su
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jaehoon
J
Shin
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chun
C
Zhong
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sabrina
http://orcid.org/0000-0002-5541-7327
S
Wang
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Prith
P
Roychowdhury
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jongseuk
J
Lim
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
David
D
Kim
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Guo-Li
GL
Ming
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hongjun
H
Song
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D004597:Electroshock; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D002843:Chromatin; D018808:Transcription Factor AP-1