title: Identification and analysis of conserved cis-regulatory regions of the MEIS1 gene.
abstract: Meis1, a conserved transcription factor of the TALE-homeodomain class, is expressed in a wide variety of tissues during development. Its complex expression pattern is likely to be controlled by an equally complex regulatory landscape. Here we have scanned the Meis1 locus for regulatory elements and found 13 non-coding regions, highly conserved between humans and teleost fishes, that have enhancer activity in stable transgenic zebrafish lines. All these regions are syntenic in most vertebrates. The composite expression of all these enhancer elements recapitulate most of Meis1 expression during early embryogenesis, indicating they comprise a basic set of regulatory elements of the Meis1 gene. Using bioinformatic tools, we identify a number of potential binding sites for transcription factors that are compatible with the regulation of these enhancers. Specifically, HHc2:066650, which is expressed in the developing retina and optic tectum, harbors several predicted Pax6 sites. Biochemical, functional and transgenic assays indicate that pax6 genes directly regulate HHc2:066650 activity.
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD) CSIC-UPO-Junta de Anadalucía, Sevilla, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Royo
authors.forename: José
authors.initials: J
authors.lastname: Bessa
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Miñán
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Tena
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Roncero
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Skarmeta
authors.forename: Fernando
authors.initials: F
authors.lastname: Casares
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D005123:Eye / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009928:Organ Specificity; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins