Abstract
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.
Highlights
Meis genes belong to the TALE-homeodomain class of conserved transcription factors
Our functional analysis of the highly conserved non-coding region (HCNR) found in the meis1 locus reveals that a large proportion of these sequences contain tissue-specific enhancers
It is likely that our screening method missed some HCNRs with enhancer activity in small expression domains, since HCNRs were pre-screened for green fluorescent protein (GFP) expression in F0
Summary
Meis genes belong to the TALE-homeodomain class of conserved transcription factors Together with their Drosophila homologue, homothorax (hth), they are known to be required for the development of many organs in vertebrates and invertebrates [1,2,3]. Meis has been detected in the somites and proximal fore- and hind-limbs at different developmental stages, as well as in the developing haematopoietic system and the pancreas [17,18,19]. This complex expression profile is likely to be controlled by an complex regulatory landscape. This paper presents a first attempt at unraveling the transcriptional regulatory complexity of the vertebrate Meis locus, identifying a number of tissue-specific CREs and predicting new potential regulators of Meis CREs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
