Meis gene expression is controlled by a deep evolutionary conserved enhancer

Resumen del póster presentado al Joint Congress of the Spanish Societies of Genetics, Cell Biology and Developmental Biology, celebrado en Gijón del 24 al 27 de octubre de 2017.-- et al.During embryonic development, the behaviour of thousand of cells must be tightly coordinated by a precise cellular crosstalk. Despite this complexity, communication between cells is orchestrated by only a few signalling pathways highly conserved across animals. In response to these pathways, different cis-regulatory elements are activated and repressed, controlling, in a spatio-temporal manner, the expression of their target genes. Although these signalling pathways have been extensively studied, our knowledge of the cis-regulatory changes associated with their activation or repression is still limited. Here, we aim to explore this issue using Danio rerio as vertebrate model. In our laboratory, we are currently manipulating different signalling pathways using agonist and antagonist molecules to further profile open chromatin regions in both treated and control embryos. Using this strategy, we have recently identified a retinoic acid (RA) responding enhancer in intron eight of the zebrafish meis2b gene. This gene encodes a TALE homeobox protein with multiple functions during vertebrate development. Sequence analysis of this enhancer reveals a strong binding site for the RA receptor, suggesting a direct control of meis2b by this signalling pathway. Using zebrafish transgenic assays, we have determined that this enhancer promotes expression in the hindbrain, a RA-dependent territory that shows strong meis2b transcription. The intron-exon organization of the Meis genes is extremely conserved during evolution. Indeed, we have found RA-responding enhancers in the same intron of most meis paralogous in zebrafish. We have also validated with 4C-seq data that some of these enhancers contact the promoter of the meis genes. Interestingly, we have also detected open chromatin regions in the equivalent introns in the amphioxus, sea urchin and flies Meis orthologous. We are currently using zebrafish enhancer assays to examine if the introns from these species contain functionally evolutionary conserved enhancers, and to determine the evolutionary origin of the Meis gene expression control by the RA signalling pathway.Peer Reviewe