Widespread transcription at neuronal activity-regulated enhancers
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Kim, Tae-Kyung
Costa, Allen M.
Wu, Jing
Laptewicz, Mike
Barbara-Haley, Kellie
Kuersten, Scott
Markenscoff-Papadimitriou, Eirene
Kuhl, Dietmar
Bito, Haruhiko
Worley, Paul F.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nature09033Metadata
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Kim, Tae-Kyung, Martin Hemberg, Jesse M. Gray, Allen M. Costa, Daniel M. Bear, Jing Wu, David A. Harmin, et al. 2010. “Widespread Transcription at Neuronal Activity-Regulated Enhancers.” Nature 465 (7295) (April 14): 182–187. doi:10.1038/nature09033.Abstract
We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. Weidentified ,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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