Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, L-F; Lin, YT; Gallegos, DA; Hazlett, MF; Gómez-Schiavon, M; Yang, MG; Kalmeta, B; Zhou, AS; Holtzman, L; Gersbach, CA; Grandl, J; Buchler, NE; West, AE

Published Date

  • January 29, 2019

Published In

Volume / Issue

  • 26 / 5

Start / End Page

  • 1174 - 1188.e5

PubMed ID

  • 30699347

Pubmed Central ID

  • 30699347

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.01.032

Language

  • eng

Conference Location

  • United States