First-time cis-regulatory interactions between mammalian-specific TFs and the zebrafish genome: Understanding first time encounters in molecular evolution

Abstract

Biological entities, whether proteins, blue whales, sensory organs or cis-regulatory elements are continuously interacting with other structures, establishing complex networks through which biological information is exchanged. These interaction networks are assembled and maintained during the course of evolution. But, what happens when new elements are incorporated for the first time into these systems? We have expressed highly divergent mammalian-specific homeodomain transcription factors (TFs), such as LEUTX and ARGFX, in the completely foreign chromatin environment of zebrafish embryos. We show that LEUTX mRNA injection disrupts early zebrafish development and embryos are arrested during early gastrulation. In the case of ARGFX, ChIP-seq experiments of injected zebrafish embryos show that the ectopic binding sites in zebrafish are preferentially found in chromatin regions that are open and accessible during zebrafish development, some of them are found in the zebrafish orthologues of ARGFX endogenous target genes in mammals. Our results suggest that biological molecular structures, such as TFs, have inherent capacities to interpret and read the information contained in other biological systems, even when these systems have not co-evolved with and are foreign to these biological structures.