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

Eukaryotic core promoters and the functional basis of transcription initiation DOI
Vanja Haberle, Alexander Stark

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 19(10), P. 621 - 637

Published: June 26, 2018

Language: Английский

Citations

633

Histone post-translational modifications — cause and consequence of genome function DOI
Gonzalo Millán-Zambrano,

Adam Burton,

Andrew J. Bannister

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 563 - 580

Published: March 25, 2022

Language: Английский

Citations

619

Epigenetic modifications of histones in cancer DOI Creative Commons
Zibo Zhao, Ali Shilatifard

Genome biology, Journal Year: 2019, Volume and Issue: 20(1)

Published: Nov. 20, 2019

Abstract The epigenetic modifications of histones are versatile marks that intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types histone biological processes with which they involved. Specifically, review enzymatic machineries involved in cancer progression, how apply currently available small molecule inhibitors for modifiers as tool compounds study functional significance their clinical implications.

Language: Английский

Citations

448

The impact of cellular metabolism on chromatin dynamics and epigenetics DOI
Michael A. Reid, Ziwei Dai, Jason W. Locasale

et al.

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(11), P. 1298 - 1306

Published: Oct. 23, 2017

Language: Английский

Citations

442

Towards a comprehensive catalogue of validated and target-linked human enhancers DOI
Molly Gasperini, Jacob M. Tome, Jay Shendure

et al.

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(5), P. 292 - 310

Published: Jan. 27, 2020

Language: Английский

Citations

316

Widespread transcriptional pausing and elongation control at enhancers DOI Open Access
Telmo Henriques, Benjamin S. Scruggs,

Michiko O. Inouye

et al.

Genes & Development, Journal Year: 2018, Volume and Issue: 32(1), P. 26 - 41

Published: Jan. 1, 2018

Regulation by gene-distal enhancers is critical for cell type-specific and condition-specific patterns of gene expression. Thus, to understand the basis activity in a given type or tissue, we must identify precise locations functionally characterize their behaviors. Here, demonstrate that transcription nearly universal feature Drosophila mammalian cells nascent RNA sequencing strategies are optimal identification both superenhancers. We dissect mechanisms governing enhancer discover remarkable similarities at protein-coding genes. show polymerase II (RNAPII) undergoes regulated pausing release enhancers. However, as compared with mRNA genes, RNAPII less stable more prone early termination. Furthermore, found level histone H3 Lys4 (H3K4) methylation corresponds transcriptional such highly active display H3K4 trimethylation rather than monomethylation considered hallmark Finally, our work provides insights into unique characteristics superenhancers, which stimulate high-level expression through rapid pause release; interestingly, this property renders associated genes resistant loss factors stabilize paused RNAPII.

Language: Английский

Citations

308

Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation DOI Creative Commons
Ryan Raisner,

Samir Kharbanda,

Lingyan Jin

et al.

Cell Reports, Journal Year: 2018, Volume and Issue: 24(7), P. 1722 - 1729

Published: Aug. 1, 2018

Acetylation of histone H3 at lysine 27 is a well-defined marker enhancer activity. However, the functional impact this modification enhancers poorly understood. Here, we use chemical genetics approach to acutely block function cAMP response element binding protein (CREB) (CBP)/P300 bromodomain in models hematological malignancies and describe consequent loss H3K27Ac specifically from enhancers, despite continued presence CBP/P300 chromatin. Using dissect role identify critical for production RNAs transcription enhancer-regulated gene networks.

Language: Английский

Citations

305

Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation DOI
Marc A. Morgan, Ali Shilatifard

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(12), P. 1271 - 1281

Published: Nov. 30, 2020

Language: Английский

Citations

289

Histone H3 lysine 4 methyltransferase KMT2D DOI

Eugene Froimchuk,

Younghoon Jang, Kai Ge

et al.

Gene, Journal Year: 2017, Volume and Issue: 627, P. 337 - 342

Published: June 29, 2017

Language: Английский

Citations

258

PRC2 is high maintenance DOI Open Access
Jia-Ray Yu, Chul‐Hwan Lee, Ozgur Oksuz

et al.

Genes & Development, Journal Year: 2019, Volume and Issue: 33(15-16), P. 903 - 935

Published: May 23, 2019

As the process that silences gene expression ensues during development, stage is set for activity of Polycomb-repressive complex 2 (PRC2) to maintain these repressed profiles. PRC2 catalyzes a specific histone posttranslational modification (hPTM) fosters chromatin compaction. also facilitates inheritance this hPTM through its self-contained “write and read” activities, key preserving cellular identity cell division. changes in occur without DNA sequence are inherited, epigenetic scope. Mutants mammalian or substrate contribute cancer other diseases, research into aberrant pathways yielding viable candidates therapeutic targeting. The effectiveness hinges on being recruited proper sites; however, resolving determinants case was not straightforward thus piqued interest many field. Here, we chronicle latest advances toward exposing high maintenance.

Language: Английский

Citations

235