期刊
NATURE
卷 465, 期 7295, 页码 182-U65出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature09033
关键词
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资金
- Nancy Lurie Marks Family Foundation
- National Institutes of Health [NS028829, R21EY019710, DP2OD006461, MH-053608]
- Lefler postdoctoral fellowship
- Jane Coffin Childs Memorial Funds
- Helen Hay Whitney postdoctoral fellowship
- Children's Hospital Ophthalmology Foundation
- Whitehall Foundation
- Klingenstein Fund
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.
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