{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":133,"searchCount":0},"additional":{"submitter":["Chen LF"],"funding":["NIDA NIH HHS","NIH HHS"],"pagination":["1174-1188.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6376993"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(5)"],"pubmed_abstract":["Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to show that Fos and Npas4 are transcribed in stochastic bursts in mouse neurons and that membrane depolarization increases mRNA expression by increasing burst frequency. We then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. Inhibiting histone acetylation reduced Fos transcription by reducing burst frequency and impaired experience-dependent Fos protein induction in the hippocampus in vivo. Thus, activity-inducible histone acetylation tunes the transcriptional dynamics of experience-regulated genes to affect selective changes in neuronal gene expression and cellular function."],"journal":["Cell reports"],"pubmed_title":["Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes."],"pmcid":["PMC6376993"],"funding_grant_id":["R33 DA041878","R01 DA036865","DP2 OD008654","R21 DA041878"],"pubmed_authors":["Lin YT","Zhou AS","Hazlett MF","Gersbach CA","West AE","Gallegos DA","Chen LF","Yang MG","Grandl J","Buchler NE","Kalmeta B","Gomez-Schiavon M","Holtzman L"],"view_count":["133"],"additional_accession":[]},"is_claimable":false,"name":"Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes.","description":"Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to show that Fos and Npas4 are transcribed in stochastic bursts in mouse neurons and that membrane depolarization increases mRNA expression by increasing burst frequency. We then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. Inhibiting histone acetylation reduced Fos transcription by reducing burst frequency and impaired experience-dependent Fos protein induction in the hippocampus in vivo. Thus, activity-inducible histone acetylation tunes the transcriptional dynamics of experience-regulated genes to affect selective changes in neuronal gene expression and cellular function.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2021-02-20T08:14:31Z","creation":"2019-03-26T22:55:53Z"},"accession":"S-EPMC6376993","cross_references":{"pubmed":["30699347"],"doi":["10.1016/j.celrep.2019.01.032"]}}