Abstract
The Runx family genes encode transcription factors that play key roles in hematopoiesis, skeletogenesis and neurogenesis and are often implicated in diseases. We describe here the cloning and characterization of Runx1, Runx2, Runx3 and Runxb genes in the elephant shark (Callorhinchus milii), a member of Chondrichthyes, the oldest living group of jawed vertebrates. Through the use of alternative promoters and/or alternative splicing, each of the elephant shark Runx genes expresses multiple isoforms similar to their orthologs in human and other bony vertebrates. The expression profiles of elephant shark Runx genes are similar to those of mammalian Runx genes. The syntenic blocks of genes at the elephant shark Runx gene loci are highly conserved in human, but represented by shorter conserved blocks in zebrafish indicating a higher degree of rearrangements in this teleost fish. Analysis of promoter regions revealed conservation of binding sites for transcription factors, including two tandem binding sites for Runx that are totally conserved in the distal promoter regions of elephant shark Runx1-3. Several conserved noncoding elements (CNEs), which are putative cis-regulatory elements, and miRNA binding sites were identified in the elephant shark and human Runx gene loci. Some of these CNEs and miRNA binding sites are absent in teleost fishes such as zebrafish and fugu. In summary, our analysis reveals that the genomic organization and expression profiles of Runx genes were already complex in the common ancestor of jawed vertebrates.
Highlights
The Runt domain transcription factor, known as the polyomavirus enhancer-binding protein 2 (PEBP2) or core-binding factor (CBF) is a heterodimer of a and b subunits
By designing primers complementary to selected exons of Runx and carrying out RTPCR and RACE using gill and kidney cDNA as templates, we were able to obtain full-length coding sequences for three elephant shark Runx a-subunit encoding genes. These sequences were mapped to the whole-genome assembly of the elephant shark [32], and their precise exon-intron boundaries, transcription start sites (TSS) and UTRs were determined (Fig. 1)
The phylogenetic analysis identified the three genes as Runx1, Runx2 and Runx3 (Fig. 2) that are located on scaffolds #152, #106 and #121, respectively
Summary
The Runt domain transcription factor, known as the polyomavirus enhancer-binding protein 2 (PEBP2) or core-binding factor (CBF) is a heterodimer of a and b subunits. Comparisons of noncoding sequences in the elephant shark and other jawed-vertebrate Runx loci were able to identify CNEs that are conserved over 450 million years of vertebrate evolution and are likely to be cis-regulatory elements.
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