title: DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees.
abstract: In honey bees (Apis mellifera), the development of a larva into either a queen or worker depends on differential feeding with royal jelly and involves epigenomic modifications by DNA methyltransferases. To understand the role of DNA methylation in this process we sequenced the larval methylomes in both queens and workers. We show that the number of differentially methylated genes (DMGs) in larval head is significantly increased relative to adult brain (2,399 vs. 560) with more than 80% of DMGs up-methylated in worker larvae. Several highly conserved metabolic and signaling pathways are enriched in methylated genes, underscoring the connection between dietary intake and metabolic flux. This includes genes related to juvenile hormone and insulin, two hormones shown previously to regulate caste determination. We also tie methylation data to expressional profiling and describe a distinct role for one of the DMGs encoding anaplastic lymphoma kinase (ALK), an important regulator of metabolism. We show that alk is not only differentially methylated and alternatively spliced in Apis, but also seems to be regulated by a cis-acting, anti-sense non-protein-coding transcript. The unusually complex regulation of ALK in Apis suggests that this protein could represent a previously unknown node in a process that activates downstream signaling according to a nutritional context. The correlation between methylation and alternative splicing of alk is consistent with the recently described mechanism involving RNA polymerase II pausing. Our study offers insights into diet-controlled development in Apis.
authors.affiliation: Australian Research Council Centre of Excellence in Coral Reef Studies,  James Cook University, Townsville, Queensland 4811,  Australia.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Foret
authors.forename: Robert
authors.initials: R
authors.lastname: Kucharski
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Suhua
authors.initials: S
authors.lastname: Feng
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Gene E
authors.initials: GE
authors.lastname: Robinson
authors.forename: Ryszard
authors.initials: R
authors.lastname: Maleszka
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D001516:Bees / Q000235:genetics*; D002952:Citric Acid Cycle / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D020869:Gene Expression Profiling; D017344:Genes, Insect / Q000235:genetics*; D006608:Hierarchy, Social; D006722:Honey; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D017381:Spliceosomes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex