title: Combinatorial activation and repression by seven transcription factors specify Drosophila odorant receptor expression.
abstract: The mechanism that specifies olfactory sensory neurons to express only one odorant receptor (OR) from a large repertoire is critical for odor discrimination but poorly understood. Here, we describe the first comprehensive analysis of OR expression regulation in Drosophila. A systematic, RNAi-mediated knock down of most of the predicted transcription factors identified an essential function of acj6, E93, Fer1, onecut, sim, xbp1, and zf30c in the regulation of more than 30 ORs. These regulatory factors are differentially expressed in antennal sensory neuron classes and specifically required for the adult expression of ORs. A systematic analysis reveals not only that combinations of these seven factors are necessary for receptor gene expression but also a prominent role for transcriptional repression in preventing ectopic receptor expression. Such regulation is supported by bioinformatics and OR promoter analyses, which uncovered a common promoter structure with distal repressive and proximal activating regions. Thus, our data provide insight into how combinatorial activation and repression can allow a small number of transcription factors to specify a large repertoire of neuron classes in the olfactory system.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Shadi
authors.initials: S
authors.lastname: Jafari
authors.forename: Liza
authors.initials: L
authors.lastname: Alkhori
authors.forename: Alexander
authors.initials: A
authors.lastname: Schleiffer
authors.forename: Anna
authors.initials: A
authors.lastname: Brochtrup
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
authors.forename: Mattias
authors.initials: M
authors.lastname: Alenius
mesh_terms: D000818:Animals; D057506:Arthropod Antennae / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D050809:POU Domain Factors; D018035:Receptors, Odorant; D014157:Transcription Factors; C095837:Eip93F protein, Drosophila; C517798:Xbp1 protein, Drosophila; C089449:sim protein, Drosophila; C068431:acj6 protein, Drosophila