Widespread transcription at neuronal activity-regulated enhancers

被引：1735

作者：

Kim, Tae-Kyung ^{[1
]}

Hemberg, Martin ^{[2
,3
]}

Gray, Jesse M. ^{[1
]}

Costa, Allen M. ^{[1
]}

Bear, Daniel M. ^{[1
]}

Wu, Jing ^{[4
]}

Harmin, David A. ^{[1
,5
]}

Laptewicz, Mike ^{[1
]}

Barbara-Haley, Kellie ^{[6
]}

Kuersten, Scott ^{[7
]}

Markenscoff-Papadimitriou, Eirene ^{[1
]}

Kuhl, Dietmar ^{[8
]}

Bito, Haruhiko ^{[9
]}

Worley, Paul F. ^{[4
]}

Kreiman, Gabriel ^{[2
,3
]}

Greenberg, Michael E. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[2] Harvard Univ, Childrens Hosp Boston, Dept Ophthalmol, Ctr Brain Sci, Boston, MA 02115 USA

[3] Harvard Univ, Swartz Ctr Theoret Neurosci, Boston, MA 02115 USA

[4] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[5] Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA

[6] Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA

[7] Epictr Biotechnol, Madison, WI 53713 USA

[8] Univ Med Ctr Hamburg Eppendorf UKE, Ctr Mol Neurobiol ZMNH, IMCC, D-20251 Hamburg, Germany

[9] Univ Tokyo, Grad Sch Med, Dept Neurochem, Bunkyo Ku, Tokyo 1130033, Japan

来源：

NATURE | 2010年 / 465卷 / 7295期

基金：

美国国家卫生研究院;

关键词：

RNA-POLYMERASE-II; CHIP-SEQ EXPERIMENTS; SYNAPSE DEVELOPMENT; GENE; ARC/ARG3.1; EXPRESSION; REVEALS; IDENTIFICATION; PLASTICITY; PROMOTERS;

D O I：

10.1038/nature09033

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified similar to 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.

引用

页码：182 / U65

页数：10

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