title: Human teneurin-1 is a direct target of the homeobox transcription factor EMX2 at a novel alternate promoter.
abstract: BACKGROUND
  Teneurin-1 is a member of a family of type II transmembrane proteins conserved from C.elegans to vertebrates. Teneurin expression in vertebrates is best studied in mouse and chicken, where the four members teneurin-1 to -4 are predominantly expressed in the developing nervous system in area specific patterns. Based on their distinct, complementary expression a possible function in the establishment of proper connectivity in the brain was postulated. However, the transcription factors contributing to these distinctive expression patterns are largely unknown. Emx2 is a homeobox transcription factor, known to be important for area specification in the developing cortex. A study of Emx2 knock-out mice suggested a role of Emx2 in regulating patterned teneurin expression.
  
  
  RESULTS
  5'RACE of human teneurin-1 revealed new alternative untranslated exons that are conserved in mouse and chicken. Closer analysis of the conserved region around the newly identified transcription start revealed promoter activity that was induced by EMX2. Mutation of a predicted homeobox binding site decreased the promoter activity in different reporter assays in vitro and in vivo in electroporated chick embryos. We show direct in vivo binding of EMX2 to the newly identified promoter element and finally confirm that the endogenous alternate transcript is specifically upregulated by EMX2.
  
  
  CONCLUSIONS
  We found that human teneurin-1 is directly regulated by EMX2 at a newly identified and conserved promoter region upstream of the published transcription start site, establishing teneurin-1 as the first human EMX2 target gene. We identify and characterize the EMX2 dependent promoter element of human teneurin-1.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Beckmann
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitobello
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ferralli
authors.forename: Daniela
authors.initials: D
authors.lastname: Kenzelmann Brož
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D018274:Electroporation; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D019063:Tenascin; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C120530:teneurin-1