Identification and analysis of conserved cis-regulatory regions of the MEIS1 gene

• Published in: PloS one Vol. 7; no. 3; p. e33617
• Main Authors: Royo, José Luis, Bessa, José, Hidalgo, Carmen, Fernández-Miñán, Ana, Tena, Juan J, Roncero, Yolanda, Gómez-Skarmeta, José Luis, Casares, Fernando
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-03-2012; Public Library of Science (PLoS)
• Subjects: Analysis; Animal genetic engineering; Animals; Animals, Genetically Modified; Binding Sites; Biology; Chromatin Immunoprecipitation; Cloning; Computational Biology; Danio rerio; DNA binding proteins; Embryogenesis; Embryonic growth stage; Enhancers; Evolution; Eye - embryology; Eye - metabolism; Eye Proteins - genetics; Eye Proteins - metabolism; Gene expression; Gene Expression Regulation, Developmental; Genes; Genomes; Genomics; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; In Situ Hybridization; MEIS1 gene; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins - genetics; Neurogenesis; Organ Specificity; Paired Box Transcription Factors - genetics; Paired Box Transcription Factors - metabolism; Pax6 protein; PAX6 Transcription Factor; Proteins; Regulatory Elements, Transcriptional; Regulatory sequences; Repressor Proteins - genetics; Repressor Proteins - metabolism; Retina; Superior colliculus; Synteny; Tectum; Tissues; Transcription (Genetics); Transcription factors; Trends; Vertebrates; Zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033617

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.