Combinatorial activation and repression by seven transcription factors specify Drosophila odorant receptor expression

PLoS Biol. 2012;10(3):e1001280. doi: 10.1371/journal.pbio.1001280. Epub 2012 Mar 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthropod Antennae / cytology
  • Arthropod Antennae / metabolism
  • Arthropod Antennae / physiology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Binding Sites
  • Computational Biology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Genes, Insect
  • Mutagenesis, Insertional
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleotide Motifs
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism
  • Promoter Regions, Genetic
  • RNA Interference
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism*
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology
  • Species Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eip93F protein, Drosophila
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • POU Domain Factors
  • Receptors, Odorant
  • Transcription Factors
  • Xbp1 protein, Drosophila
  • sim protein, Drosophila
  • acj6 protein, Drosophila