Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes DOI Creative Commons

Liang-Fu Chen,

Yen Ting Lin, David A. Gallegos

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 26(5), P. 1174 - 1188.e5

Published: Jan. 1, 2019

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters enhancers of activity-regulated genes. Exactly how modulates these genes has remained unknown. We used single-cell situ transcriptional analysis to show that Fos Npas4 are transcribed stochastic bursts mouse neurons membrane depolarization mRNA expression by increasing burst frequency. then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins mimic block activity-induced locally enhancers. Adding increased prolonging duration resulted higher protein levels an elevation resting potential. Inhibiting reduced reducing frequency impaired experience-dependent induction the hippocampus vivo. Thus, tunes dynamics experience-regulated affect selective changes neuronal cellular function.

Language: Английский

Histone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers DOI Open Access
Jian Yan,

Shi-An A. Chen,

Andrea Local

et al.

Cell Research, Journal Year: 2018, Volume and Issue: 28(2), P. 204 - 220

Published: Jan. 9, 2018

Language: Английский

Citations

171

Enhancer Logic and Mechanics in Development and Disease DOI

Ryan Rickels,

Ali Shilatifard

Trends in Cell Biology, Journal Year: 2018, Volume and Issue: 28(8), P. 608 - 630

Published: May 11, 2018

Language: Английский

Citations

167

Deciphering the multi-scale, quantitative cis-regulatory code DOI Creative Commons
Seungsoo Kim, Joanna Wysocka

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(3), P. 373 - 392

Published: Jan. 23, 2023

Uncovering the cis-regulatory code that governs when and how much each gene is transcribed in a given genome cellular state remains central goal of biology. Here, we discuss major layers regulation influence transcriptional outputs are encoded by DNA sequence context. We first transcription factors bind specific sequences dosage-dependent cooperative manner then proceed to cofactors facilitate factor function mediate activity modular elements such as enhancers, silencers, promoters. consider complex poorly understood interplay these diverse within regulatory landscapes its relationships with chromatin states nuclear organization. propose mechanistically informed, quantitative model integrates multiple will be key ultimately cracking code.

Language: Английский

Citations

167

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes DOI Creative Commons
Tasnim H. Beacon,

Geneviève P. Delcuve,

Camila López

et al.

Clinical Epigenetics, Journal Year: 2021, Volume and Issue: 13(1)

Published: July 8, 2021

Abstract Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark typically restricted to narrow regions the 5`end gene body, though a small subset genes have broad H3K4me3 domain which extensively covers coding region. Although most studies focus on mark, associated with plethora modifications (e.g., acetylated K27) therein termed domain. Genes are involved in cell identity essential functions clinical potential as biomarkers for patient stratification. Reducing expression may increase metastatic cancer cells. Enhancers super-enhancers interact forming hub interactions involving nucleosome-depleted regions. Together, regulatory elements coalesce factors, modifying/remodeling enzymes, coactivators, Mediator and/or Integrator complex into factory be analogous liquid–liquid phase-separated condensate. The has dynamic structure supports frequent bursts. In this review, we present current knowledge domains.

Language: Английский

Citations

158

Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes DOI Creative Commons

Liang-Fu Chen,

Yen Ting Lin, David A. Gallegos

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 26(5), P. 1174 - 1188.e5

Published: Jan. 1, 2019

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters enhancers of activity-regulated genes. Exactly how modulates these genes has remained unknown. We used single-cell situ transcriptional analysis to show that Fos Npas4 are transcribed stochastic bursts mouse neurons membrane depolarization mRNA expression by increasing burst frequency. then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins mimic block activity-induced locally enhancers. Adding increased prolonging duration resulted higher protein levels an elevation resting potential. Inhibiting reduced reducing frequency impaired experience-dependent induction the hippocampus vivo. Thus, tunes dynamics experience-regulated affect selective changes neuronal cellular function.

Language: Английский

Citations

150