Publication Date:
2010-04-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020079/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020079/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- DP2OD006461/OD/NIH HHS/ -- MH-053608/MH/NIMH NIH HHS/ -- NS028829/NS/NINDS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30 HD018655-25/HD/NICHD NIH HHS/ -- P30 HD018655-26/HD/NICHD NIH HHS/ -- P30 HD018655-27/HD/NICHD NIH HHS/ -- R01 NS028829/NS/NINDS NIH HHS/ -- R21EY019710/EY/NEI NIH HHS/ -- R37 NS028829/NS/NINDS NIH HHS/ -- R37 NS028829-12/NS/NINDS NIH HHS/ -- R37 NS028829-13/NS/NINDS NIH HHS/ -- R37 NS028829-14/NS/NINDS NIH HHS/ -- R37 NS028829-15/NS/NINDS NIH HHS/ -- R37 NS028829-16/NS/NINDS NIH HHS/ -- R37 NS028829-17/NS/NINDS NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):182-7. doi: 10.1038/nature09033. Epub 2010 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393465" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics
;
CREB-Binding Protein/metabolism
;
Consensus Sequence/genetics
;
Cytoskeletal Proteins/genetics
;
Enhancer Elements, Genetic/*genetics
;
Gene Expression Regulation/*genetics
;
Genes, Reporter
;
Genes, fos/genetics
;
Histones/metabolism
;
Methylation
;
Mice
;
Mice, Inbred C57BL
;
Nerve Tissue Proteins/genetics
;
Neurons/*metabolism
;
RNA Polymerase II/metabolism
;
RNA, Untranslated/biosynthesis/genetics
;
Transcription, Genetic/*genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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