Conserved Non-Coding Element Derived Regulation of the Meis2.2 Homeobox Gene During Embryonic Development

The homeobox-containing Meis gene family includes at least four members that are expressed in spatially and temporally conserved fashion throughout development in all vertebrates examined thus far. Products of the Meis genes function as cofactors, interacting with other transcription factors and DNA to assist in the regulation of transcription. Most importantly, they appear to work with the Hox proteins as well as other homeobox genes’ products including Pbx proteins. At this time, little is known about the regulation of the Meis genes. Using phylogenetic footprinting to search for regulatory elements in association with the Meis family of homeobox-containing genes, we identified a highly conserved element located downstream of the Meis2 gene that we have called Meis2 Downstream Element 1 (m2de1). This putative enhancer is conserved in sequence and position across the genomes of all vertebrates examined. Furthermore, the m2de1 element contains several putative transcription factor binding sites. In this study, we have demonstrated the ability of m2de1 to drive reporter gene expression through microinjection derived transgenic analysis. Reporter gene expression was observed in the developing brain of zebrafish embryos in a manner consistent with endogenous Meis2 expression, potentially implicating the m2de1 element with cis-regulatory function.