title: Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation.
abstract: Class I Basic Helix-Loop-Helix (bHLH) transcription factors form homodimers or heterodimers with class II bHLH proteins. While bHLH heterodimers are known to have diverse roles, little is known about the role of class I homodimers. In this manuscript, we show that a linked dimer of Daughterless (Da), the only Drosophila class I bHLH protein, activates Atonal (Ato) expression and retinal neuron differentiation synergistically with the retinal determination factor Eyeless (Ey). The HLH protein Extramacrocheate (Emc), which forms heterodimer with Da, antagonizes the synergistic activation from Da but not the Da-Da linked dimer with Ey. We show that Da directly interacts with Ey and promotes Ey binding to the Ey binding site in the Ato 3׳ enhancer. Interestingly, the Ey binding site in the Ato 3׳ enhancer contains an embedded E-box that is also required for the synergistic activation by Ey and Da. Finally we show that mammalian homologs of Ey and Da can functionally replace their Drosophila counterparts to synergistically activate the Ato enhancer, suggesting that the observed function is evolutionary conserved.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Miho
authors.initials: M
authors.lastname: Tanaka-Matakatsu
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: John
authors.initials: J
authors.lastname: Miller
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Borger
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: wei@uchicago.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D060227:Imaginal Discs / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055351:Retinal Neurons / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C090080:Da protein, Drosophila; C082142:ato protein, Drosophila; C113278:ey protein, Drosophila
keywords: Atonal; Daughterless; Drosophila eye development; Eyeless; Pax6; bHLH proteins