The Drosophila tango gene encodes a bHLH-PAS protein that is orthologous to mammalian Arnt and controls CNS midline and tracheal development.

The Drosophila single-minded and trachealess bHLH-PAS genes control transcription and development of the CNS midline cell lineage and tracheal tubules, respectively. We show that Single-minded and Trachealess activate transcription by forming dimers with the Drosophila Tango protein that is an orthologue of the mammalian Arnt protein. Both cell culture and in vivo studies show that a DNA enhancer element acts as a binding site for both Single-minded::Tango and Trachealess::Tango heterodimers and functions in controlling CNS midline and tracheal transcription. Isolation and analysis of tango mutants reveal CNS midline and tracheal defects, and gene dosage studies demonstrate in vivo interactions between single-minded::tango and trachealess::tango. These experiments support the existence of an evolutionarily conserved, functionally diverse bHLH-PAS protein regulatory system.

[1]  Christian Klämbt,et al.  The midline of the drosophila central nervous system: A model for the genetic analysis of cell fate, cell migration, and growth cone guidance , 1991, Cell.

[2]  B. Abbott,et al.  Developmental expression of two members of a new class of transcription factors: II. Expression of aryl hydrocarbon receptor nuclear translocator in the C57BL/6N mouse embryo , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[3]  O. Hankinson,et al.  Cloning of a factor required for activity of the Ah (dioxin) receptor. , 1991, Science.

[4]  J. Nambu,et al.  Alternate functions of the single-minded and rhomboid genes in development of the Drosophila ventral neuroectoderm , 1996, Mechanisms of Development.

[5]  Y. Fujii‐Kuriyama,et al.  Possible function of Ah receptor nuclear translocator (Arnt) homodimer in transcriptional regulation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[6]  B. Shilo,et al.  trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. , 1996, Genes & development.

[7]  O. Hankinson,et al.  Identification of Functional Domains of the Aryl Hydrocarbon Receptor (*) , 1995, The Journal of Biological Chemistry.

[8]  L. Birnbaum,et al.  Developmental expression of two members of a new class of transcription factors: I. Expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[9]  B. Ebert,et al.  Drosophila melanogaster SL2 cells contain a hypoxically inducible DNA binding complex which recognises mammalian HIF‐1 binding sites , 1996, FEBS letters.

[10]  J. Michaud,et al.  Single-minded--two genes, three chromosomes. , 1997, Genome research.

[11]  M. Gassmann,et al.  Functional interference between hypoxia and dioxin signal transduction pathways: competition for recruitment of the Arnt transcription factor , 1996, Molecular and cellular biology.

[12]  Wei Chen,et al.  The Drosophila melanogaster similar bHLH-PAS gene encodes a protein related to human hypoxia-inducible factor 1 alpha and Drosophila single-minded. , 1996, Gene.

[13]  B. Necela,et al.  Isolation and Expression of cDNAs from Rainbow Trout (Oncorhynchus mykiss) That Encode Two Novel Basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH/PAS) Proteins with Distinct Functions in the Presence of the Aryl Hydrocarbon Receptor , 1996, The Journal of Biological Chemistry.

[14]  V. Hartenstein,et al.  The role of the tracheae and musculature during pathfinding of Drosophila embryonic sensory axons. , 1993, Developmental biology.

[15]  M. Rosbash,et al.  PAS is a dimerization domain common to Drosophila Period and several transcription factors , 1993, Nature.

[16]  M. Levine,et al.  Synergistic activation and repression of transcription by Drosophila homeobox proteins , 1989, Cell.

[17]  Stephen T. Crews,et al.  The single-minded gene of Drosophila is required for the expression of genes important for the development of CNS midline cells , 1990, Cell.

[18]  M. Noll,et al.  Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network , 1986, Cell.

[19]  H. Swanson,et al.  DNA Binding Specificities and Pairing Rules of the Ah Receptor, ARNT, and SIM Proteins (*) , 1995, The Journal of Biological Chemistry.

[20]  O. Hankinson.  The aryl hydrocarbon receptor complex. , 1995, Annual review of pharmacology and toxicology.

[21]  M. Nirenberg,et al.  Dorsal-ventral patterning genes restrict NK-2 homeobox gene expression to the ventral half of the central nervous system of Drosophila embryos. , 1995, Developmental biology.

[22]  S. Crews,et al.  Transcriptional activation domains of the single-minded bHLH protein are required for CNS midline cell development , 1994, Mechanisms of Development.

[23]  N. Patel,et al.  Characterization and cloning of fasciclin III: A glycoprotein expressed on a subset of neurons and axon pathways in Drosophila , 1987, Cell.

[24]  L. Goldstein,et al.  An inverse PCR screen for the detection of P element insertions in cloned genomic intervals in Drosophila melanogaster. , 1995, Genetics.

[25]  B. Shilo,et al.  breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. , 1992, Genes & development.

[26]  J. Hogenesch,et al.  Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway* , 1997, The Journal of Biological Chemistry.

[27]  S. Crews,et al.  Control of CNS midline transcription by asymmetric E-box-like elements: similarity to xenobiotic responsive regulation. , 1994, Development.

[28]  G. Semenza,et al.  Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. Laughon,et al.  The Drosophila neuralized gene encodes a C3HC4 zinc finger. , 1993, The EMBO journal.

[30]  A. Spradling,et al.  Preferential transposition of Drosophila P elements to nearby chromosomal sites. , 1993, Genetics.

[31]  J. Jacobs,et al.  Mesectodermal cell fate analysis in Drosophila midline mutants , 1994, Mechanisms of Development.

[32]  B. Necela,et al.  Isolation and Expression of cDNAs from Rainbow Trout ( Oncorhynchus mykiss ) That Encode Two Novel , 1996 .

[33]  D. Andrew,et al.  Tubulogenesis in Drosophila: a requirement for the trachealess gene product. , 1996, Genes & development.

[34]  Stephen T. Crews,et al.  Molecular genetics of the single-minded locus: A gene involved in the development of the Drosophila nervous system , 1988, Cell.

[35]  Minoru Tanaka,et al.  Positional Cloning of the Mouse Circadian Clock Gene , 1997, Cell.

[36]  S. McKnight,et al.  Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. , 1997, Genes & development.

[37]  David Baunoch,et al.  Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT , 1997, Nature.

[38]  L. Poellinger,et al.  Protein‐protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor‐Arnt transcription factor complex. , 1995, The EMBO journal.

[39]  R. Tjian,et al.  Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. , 1989, Science.

[40]  S. Jain,et al.  Potent transactivation domains of the Ah receptor and the Ah receptor nuclear translocator map to their carboxyl termini. , 1994, The Journal of biological chemistry.

[41]  A. Laughon,et al.  Molecular and genetic characterization of the Drosophila tartan gene. , 1993, Developmental biology.

[42]  Y. Jan,et al.  The Drosophila neurogenic gene neuralized encodes a novel protein and is expressed in precursors of larval and adult neurons. , 1991, The EMBO journal.

[43]  O. Gotoh,et al.  cDNA Cloning and Tissue-Specific Expression of a Novel Basic Helix-Loop-Helix/PAS Factor (Arnt2) with Close Sequence Similarity to the Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) , 1996 .

[44]  Stephen T. Crews,et al.  The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development , 1991, Cell.

[45]  H. Li,et al.  Transcriptional activation function of the mouse Ah receptor nuclear translocator. , 1994, The Journal of biological chemistry.

[46]  Stephen T. Crews,et al.  CNS midline enhancers of the Drosophila slit and Toll genes , 1993, Mechanisms of Development.