Osceola Whitney, Andreas R. Pfenning, Jason T. Howard, Charles A Blatti, Fang Liu, James M.Ward, Rui Wang, Jean-Nicolas Audet, Manolis Kellis, Sayan Mukherjee, Saurabh Sinha, Alexander J. Hartemink, Anne E. West, and Erich D. Jarvis, 'Core and Region Enriched Networks of Behaviorally Regulated Genes and the Singing Genome', Science (2014).
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 has strong parallels with those that mediate human speech. We found that ~10% of genes in the avian genome were regulated by singing, and 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 (TF), their binding motifs and pre-singing H3K27ac enhancer activity in the regulatory regions of the associated genes. RNAi 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 pre-defined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks.