Widespread transcription at neuronal activity-regulated enhancers

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

Research output: Contribution to journalArticle

1234 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)182-187
Number of pages6
JournalNature
Volume465
Issue number7295
DOIs
StatePublished - May 13 2010

Fingerprint

RNA Polymerase II
RNA
Messenger RNA
Histones
Lysine
Genome
Neurons
Genes

ASJC Scopus subject areas

  • General

Cite this

Kim, T. K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., ... Greenberg, M. E. (2010). Widespread transcription at neuronal activity-regulated enhancers. Nature, 465(7295), 182-187. https://doi.org/10.1038/nature09033

Widespread transcription at neuronal activity-regulated enhancers. / Kim, Tae Kyung; Hemberg, Martin; Gray, Jesse M.; Costa, Allen M.; Bear, Daniel M.; Wu, Jing; Harmin, David A.; Laptewicz, Mike; Barbara-Haley, Kellie; Kuersten, Scott; Markenscoff-Papadimitriou, Eirene; Kuhl, Dietmar; Bito, Haruhiko; Worley, Paul F.; Kreiman, Gabriel; Greenberg, Michael E.

In: Nature, Vol. 465, No. 7295, 13.05.2010, p. 182-187.

Research output: Contribution to journalArticle

Kim, TK, Hemberg, M, Gray, JM, Costa, AM, Bear, DM, Wu, J, Harmin, DA, Laptewicz, M, Barbara-Haley, K, Kuersten, S, Markenscoff-Papadimitriou, E, Kuhl, D, Bito, H, Worley, PF, Kreiman, G & Greenberg, ME 2010, 'Widespread transcription at neuronal activity-regulated enhancers', Nature, vol. 465, no. 7295, pp. 182-187. https://doi.org/10.1038/nature09033
Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010 May 13;465(7295):182-187. https://doi.org/10.1038/nature09033
Kim, Tae Kyung ; Hemberg, Martin ; Gray, Jesse M. ; Costa, Allen M. ; Bear, Daniel M. ; Wu, Jing ; Harmin, David A. ; Laptewicz, Mike ; Barbara-Haley, Kellie ; Kuersten, Scott ; Markenscoff-Papadimitriou, Eirene ; Kuhl, Dietmar ; Bito, Haruhiko ; Worley, Paul F. ; Kreiman, Gabriel ; Greenberg, Michael E. / Widespread transcription at neuronal activity-regulated enhancers. In: Nature. 2010 ; Vol. 465, No. 7295. pp. 182-187.
@article{4333512b6b194779902ebfe5324a3347,
title = "Widespread transcription at neuronal activity-regulated enhancers",
abstract = "We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified ∼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.",
author = "Kim, {Tae Kyung} and Martin Hemberg and Gray, {Jesse M.} and Costa, {Allen M.} and Bear, {Daniel M.} and Jing Wu and Harmin, {David A.} and Mike Laptewicz and Kellie Barbara-Haley and Scott Kuersten and Eirene Markenscoff-Papadimitriou and Dietmar Kuhl and Haruhiko Bito and Worley, {Paul F.} and Gabriel Kreiman and Greenberg, {Michael E.}",
year = "2010",
month = "5",
day = "13",
doi = "10.1038/nature09033",
language = "English (US)",
volume = "465",
pages = "182--187",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7295",

}

TY - JOUR

T1 - Widespread transcription at neuronal activity-regulated enhancers

AU - Kim, Tae Kyung

AU - Hemberg, Martin

AU - Gray, Jesse M.

AU - Costa, Allen M.

AU - Bear, Daniel M.

AU - Wu, Jing

AU - Harmin, David A.

AU - Laptewicz, Mike

AU - Barbara-Haley, Kellie

AU - Kuersten, Scott

AU - Markenscoff-Papadimitriou, Eirene

AU - Kuhl, Dietmar

AU - Bito, Haruhiko

AU - Worley, Paul F.

AU - Kreiman, Gabriel

AU - Greenberg, Michael E.

PY - 2010/5/13

Y1 - 2010/5/13

N2 - We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified ∼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.

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

UR - http://www.scopus.com/inward/record.url?scp=77952367798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952367798&partnerID=8YFLogxK

U2 - 10.1038/nature09033

DO - 10.1038/nature09033

M3 - Article

VL - 465

SP - 182

EP - 187

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7295

ER -