Widespread Transcription at Neuronal Activity-regulated Enhancers

Overview

Journal Nature

Specialty Science

Date 2010 Apr 16

PMID 20393465

Citations 1395

Authors

Tae-Kyung Kim

Martin Hemberg

Jesse M Gray

Allen M Costa

Daniel M Bear

Jing Wu

David A Harmin

Mike Laptewicz

Kellie Barbara-Haley

Scott Kuersten

Eirene Markenscoff-Papadimitriou

Dietmar Kuhl

Haruhiko Bito

Paul F Worley

Gabriel Kreiman

Michael E Greenberg

Affiliations

Soon will be listed here.

Abstract

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

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