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Science. 2014 Dec 12;346(6215):1256780. doi: 10.1126/science.1256780.

Core and region-enriched networks of behaviorally regulated genes and the singing genome.

Author information

1
Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu.
2
Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. Computer Science and Artificial Intelligence Laboratory and the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu.
3
Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA.
4
Department of Computer Science, University of Illinois, Urbana-Champaign, IL, USA.
5
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
6
Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
7
Computer Science and Artificial Intelligence Laboratory and the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8
Department of Statistics, Duke University, Durham, NC, USA.
9
Department of Computer Science, Duke University, Durham, NC 27708-0129, USA.
10
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu.

Abstract

Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks.

PMID:
25504732
PMCID:
PMC4359888
DOI:
10.1126/science.1256780
[Indexed for MEDLINE]
Free PMC Article

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