Identification of Gene Regulatory Elements Associated With the Meis Family of Homeobox Genes

Homologs of the Meis homeobox-containing gene family (myeloid ecotropic leukemia virus integration site) have been identified in all animals studied. The products of the Meis genes appear to function as cofactors, interacting with other transcription factors and DNA facilitating transcriptional regulation. Most notably, they appear to act as co-factors of Hox proteins and have also been described as acting with other homeobox genes. The vertebrate Meis homeobox-containing gene family consists of at least three members, and while little to nothing is known about their regulation, they are expressed in conserved patterns throughout the embryonic development of those vertebrates that have been examined. Using comparative genomics/phylogenetic footprinting to search for regulatory elements associated with the Meis family of homeobox-containing genes, 4 highly conserved elements located downstream of the Meis2 gene have been identified. They are well-conserved in sequence and relative position amongst the genomes of all vertebrates examined, including human, mouse, chicken, zebrafish and the pufferfish Takifugu rubripes. All elements, named m2de1 (Meis 2 Downstream Element), m2de2, m2de3, and m2de4, contain several putative transcription factor binding sites. Conservation in sequence and position indicate the m2de1, m2de2, m2de3, and m2de4 elements most likely play some important role in animals as cis-regulatory elements.