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Identification and Analysis of Conserved cis-Regulatory Regions of the MEIS1 Gene
Royo Sánchez-Palencia, José Luis; Bessa, José; Hidalgo, Carmen; Fernández-Miñán, Ana; Tena Aguilar, Juan Jesús; Roncero, Yolanda; Gómez-Skarmeta, José Luis; Casares, Fernando
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. This work was funded through grants BFU2009-07044 (MICINN) and Proyecto de Excelencia CVI 2658 (Junta de Andalucía) to FC and BFU2010-14839 (MICINN), CSD2007-00008 and Proyecto de Excelencia CVI-3488 to JLGS. JLR is a recipient of a JAE-DOC contract from the Spanish National Research Council (CSIC).
cc-by (c) José Luis Royo et al., 2018
http://creativecommons.org/licenses/by/4.0/
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