title: Chromatin modification of Notch targets in olfactory receptor neuron diversification.
abstract: Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal. Each ORN in Drosophila acquires one of three basic identities defined by the compound outcome of three iterated Notch signaling events during neurogenesis. Hamlet, the Drosophila Evi1 and Prdm16 proto-oncogene homolog, modifies cellular responses to these iteratively used Notch signals in a context-dependent manner, and controls odorant receptor gene choice and ORN axon targeting specificity. In nascent ORNs, Hamlet erases the Notch state inherited from the parental cell, enabling a modified response in a subsequent round of Notch signaling. Hamlet directs locus-specific modifications of histone methylation and histone density and controls accessibility of the DNA-binding protein Suppressor of Hairless at the Notch target promoter.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Endo
authors.forename: M Rezaul
authors.initials: MR
authors.lastname: Karim
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Alena
authors.initials: A
authors.lastname: Krejci
authors.forename: Emi
authors.initials: E
authors.lastname: Kinameri
authors.forename: Matthias
authors.initials: M
authors.lastname: Siebert
authors.forename: Kei
authors.initials: K
authors.lastname: Ito
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bray
authors.forename: Adrian W
authors.initials: AW
authors.lastname: Moore
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology* / Q000254:growth & development; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D018035:Receptors, Odorant / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C464822:HAM protein, Drosophila; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D018035:Receptors, Odorant; D014157:Transcription Factors; D049452:Green Fluorescent Proteins