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Sci Rep. 2015 Jun 15;5:11136. doi: 10.1038/srep11136.

Insights into the Transcriptional Architecture of Behavioral Plasticity in the Honey Bee Apis mellifera.

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Computational Bioscience Research Center, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Departments of Entomology and Institute for Genomic Biology, Urbana, IL 61801; and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Lumenogix Inc., 2935 Rodeo Park Drive East, Santa Fe NM, 87505, USA.
DNAFORM Inc., Leading Venture Plaza-2, 75-1, Ono-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0046, Japan.
1] DNAFORM Inc., Leading Venture Plaza-2, 75-1, Ono-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0046, Japan [2] RIKEN Center for Life Science Technologies, Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.


Honey bee colonies exhibit an age-related division of labor, with worker bees performing discrete sets of behaviors throughout their lifespan. These behavioral states are associated with distinct brain transcriptomic states, yet little is known about the regulatory mechanisms governing them. We used CAGEscan (a variant of the Cap Analysis of Gene Expression technique) for the first time to characterize the promoter regions of differentially expressed brain genes during two behavioral states (brood care (aka "nursing") and foraging) and identified transcription factors (TFs) that may govern their expression. More than half of the differentially expressed TFs were associated with motifs enriched in the promoter regions of differentially expressed genes (DEGs), suggesting they are regulators of behavioral state. Strikingly, five TFs (nf-kb, egr, pax6, hairy, and clockwork orange) were predicted to co-regulate nearly half of the genes that were upregulated in foragers. Finally, differences in alternative TSS usage between nurses and foragers were detected upstream of 646 genes, whose functional analysis revealed enrichment for Gene Ontology terms associated with neural function and plasticity. This demonstrates for the first time that alternative TSSs are associated with stable differences in behavior, suggesting they may play a role in organizing behavioral state.

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