title: Core and region-enriched networks of behaviorally regulated genes and the singing genome.
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.
authors.affiliation: 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.
authors.forename: Osceola
authors.initials: O
authors.lastname: Whitney
authors.affiliation: 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.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Pfenning
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Howard
authors.affiliation: Department of Computer Science, University of Illinois, Urbana-Champaign, IL, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Blatti
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ward
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Jean-Nicoles
authors.initials: JN
authors.lastname: Audet
authors.affiliation: Computer Science and Artificial Intelligence Laboratory and the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Department of Statistics, Duke University, Durham, NC, USA.
authors.forename: Sayan
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Computer Science, University of Illinois, Urbana-Champaign, IL, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Computer Science, Duke University, Durham, NC 27708-0129, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Hartemink
authors.affiliation: 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.
authors.forename: Anne E
authors.initials: AE
authors.lastname: West
authors.affiliation: 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.
authors.forename: Erich D
authors.initials: ED
authors.lastname: Jarvis
mesh_terms: D000107:Acetylation; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D046369:Finches / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016678:Genome; D006657:Histones / Q000378:metabolism; D008297:Male; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014828:Vocalization, Animal
chemical_list: D030161:Avian Proteins; D006657:Histones; D014157:Transcription Factors