Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.
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.
|Year of Publication||
|PubMed Central ID||
R37 NS028829 / NS / NINDS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
Howard Hughes Medical Institute / United States
32CA009361 / CA / NCI NIH HHS / United States
T32GM007753 / GM / NIGMS NIH HHS / United States
T32 CA009361 / CA / NCI NIH HHS / United States
5R37NS028829-25 / NS / NINDS NIH HHS / United States