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Nat Neurosci. 2014 Oct;17(10):1330-9. doi: 10.1038/nn.3808. Epub 2014 Sep 7.

Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.

Author information

1
1] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] MD-PhD Program, Harvard Medical School, Boston, Massachusetts, USA. [3] Division of Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Ophthalmology, Children's Hospital Boston, Harvard University, Boston, Massachusetts, USA.
4
1] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
5
1] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Abstract

Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in mouse cortical neurons. We find that the subset of enhancers enriched for monomethylation of histone H3 Lys4 (H3K4me1) and binding of the transcriptional coactivator CREBBP (also called CBP) that shows increased acetylation of histone H3 Lys27 (H3K27ac) after membrane depolarization of cortical neurons functions to regulate activity-dependent transcription. A subset of these enhancers appears to require binding of FOS, which was previously thought to bind primarily to promoters. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function and provide a resource of functional cis-regulatory elements that may give insight into the genetic variants that contribute to brain development and disease.

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PMID:
25195102
PMCID:
PMC4297619
DOI:
10.1038/nn.3808
[Indexed for MEDLINE]
Free PMC Article

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