title: Insights into the Transcriptional Architecture of Behavioral Plasticity in the Honey Bee Apis mellifera.
abstract: 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.
authors.affiliation: 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.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Khamis
authors.affiliation: Departments of Entomology and Institute for Genomic Biology, Urbana, IL 61801; and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Hamilton
authors.affiliation: 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.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Medvedeva
authors.affiliation: 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.
authors.forename: Tanvir
authors.initials: T
authors.lastname: Alam
authors.affiliation: 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.
authors.forename: Intikhab
authors.initials: I
authors.lastname: Alam
authors.affiliation: 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.
authors.forename: Magbubah
authors.initials: M
authors.lastname: Essack
authors.affiliation: Lumenogix Inc., 2935 Rodeo Park Drive East, Santa Fe NM, 87505, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Umylny
authors.affiliation: 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.
authors.forename: Boris R
authors.initials: BR
authors.lastname: Jankovic
authors.affiliation: Departments of Entomology and Institute for Genomic Biology, Urbana, IL 61801; and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Naeger
authors.affiliation: DNAFORM Inc., Leading Venture Plaza-2, 75-1, Ono-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0046, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: 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.
authors.forename: Matthias
authors.initials: M
authors.lastname: Harbers
authors.affiliation: Departments of Entomology and Institute for Genomic Biology, Urbana, IL 61801; and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
authors.forename: Gene E
authors.initials: GE
authors.lastname: Robinson
authors.affiliation: 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.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bajic
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001516:Bees / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D051765:Early Growth Response Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051765:Early Growth Response Transcription Factors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D016328:NF-kappa B; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C061841:hairy protein, insect