title: Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex.
abstract: In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb-MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO(2)) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO(2) receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map.
authors.affiliation: Department of Pathology, Stanford University, Stanford, California 94305, USA.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Sim
authors.forename: Sarah
authors.initials: S
authors.lastname: Perry
authors.forename: Sana Khalid
authors.initials: SK
authors.lastname: Tharadra
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Lipsick
authors.forename: Anandasankar
authors.initials: A
authors.lastname: Ray
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000235:genetics; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C516369:Gr21a protein, Drosophila; C516368:Gr63a protein, Drosophila; D006570:Heterochromatin; C467519:Myb protein, Drosophila; D020598:Proto-Oncogene Proteins c-myb; D011956:Receptors, Cell Surface; D018035:Receptors, Odorant; C054079:carbon dioxide receptor; D020169:Caspases; C438246:STRICA protein, Drosophila