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Runx family genes in a cartilaginous fish, the elephant shark (Callorhinchus milii).

Nah GS, Lim ZW, Tay BH, Osato M, Venkatesh B - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

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.

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Synteny of genes in the Runx loci of elephant shark and selected bony vertebrates.(A) Runx1 locus, (B) Runx2 locus and (C) Runx3 locus. Genes are represented by arrows. Genes with conserved synteny are coloured. Clusters of some non-syntenic genes are represented as white boxes and labelled in brackets. The gene order is from Ensembl (www.ensembl.org) and the elephant shark genome assembly (http://esharkgenome.imcb.a-star.edu.sg/).
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pone-0093816-g003: Synteny of genes in the Runx loci of elephant shark and selected bony vertebrates.(A) Runx1 locus, (B) Runx2 locus and (C) Runx3 locus. Genes are represented by arrows. Genes with conserved synteny are coloured. Clusters of some non-syntenic genes are represented as white boxes and labelled in brackets. The gene order is from Ensembl (www.ensembl.org) and the elephant shark genome assembly (http://esharkgenome.imcb.a-star.edu.sg/).

Mentions: The availability of the whole-genome sequence of elephant shark enabled us to compare the synteny of genes at Runx loci in elephant shark and other sequenced vertebrate genomes. The synteny of genes at the elephant shark Runx1, Runx2 and Runx3 loci is highly conserved in tetrapods (Fig. 3). A comparison of syntenic genes across the three Runx gene loci indicates that paralogs of Clic and Rcan genes are present in all three Runx gene loci. This indicates that three Runx gene loci in the jawed vertebrates are the result of duplication of an ancestral locus that comprised Runx, Clic and Rcan genes in that order. Of note are the characteristic “interlocked” gene structures of Runx2 and Supt3h in all the jawed vertebrates, except the duplicated locus in zebrafish (Runx2b locus) in which Supt3h has been lost. Indeed, a Supt3h gene resides next to Runt gene in the genome of the most basally branching chordate, the amphioxus (chrUn: 270,089,714–270,297,951; Mar 2006-JGI1.0/braFlo1) indicating that their linkage is an ancient feature. It can therefore be inferred that linkage of Supt3h to Runt gene was retained in the jawed vertebrate Runx2 locus whereas the paralogs of Supt3h in Runx1 and Runx3 loci were lost secondarily.


Runx family genes in a cartilaginous fish, the elephant shark (Callorhinchus milii).

Nah GS, Lim ZW, Tay BH, Osato M, Venkatesh B - PLoS ONE (2014)

Synteny of genes in the Runx loci of elephant shark and selected bony vertebrates.(A) Runx1 locus, (B) Runx2 locus and (C) Runx3 locus. Genes are represented by arrows. Genes with conserved synteny are coloured. Clusters of some non-syntenic genes are represented as white boxes and labelled in brackets. The gene order is from Ensembl (www.ensembl.org) and the elephant shark genome assembly (http://esharkgenome.imcb.a-star.edu.sg/).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3974841&req=5

pone-0093816-g003: Synteny of genes in the Runx loci of elephant shark and selected bony vertebrates.(A) Runx1 locus, (B) Runx2 locus and (C) Runx3 locus. Genes are represented by arrows. Genes with conserved synteny are coloured. Clusters of some non-syntenic genes are represented as white boxes and labelled in brackets. The gene order is from Ensembl (www.ensembl.org) and the elephant shark genome assembly (http://esharkgenome.imcb.a-star.edu.sg/).
Mentions: The availability of the whole-genome sequence of elephant shark enabled us to compare the synteny of genes at Runx loci in elephant shark and other sequenced vertebrate genomes. The synteny of genes at the elephant shark Runx1, Runx2 and Runx3 loci is highly conserved in tetrapods (Fig. 3). A comparison of syntenic genes across the three Runx gene loci indicates that paralogs of Clic and Rcan genes are present in all three Runx gene loci. This indicates that three Runx gene loci in the jawed vertebrates are the result of duplication of an ancestral locus that comprised Runx, Clic and Rcan genes in that order. Of note are the characteristic “interlocked” gene structures of Runx2 and Supt3h in all the jawed vertebrates, except the duplicated locus in zebrafish (Runx2b locus) in which Supt3h has been lost. Indeed, a Supt3h gene resides next to Runt gene in the genome of the most basally branching chordate, the amphioxus (chrUn: 270,089,714–270,297,951; Mar 2006-JGI1.0/braFlo1) indicating that their linkage is an ancient feature. It can therefore be inferred that linkage of Supt3h to Runt gene was retained in the jawed vertebrate Runx2 locus whereas the paralogs of Supt3h in Runx1 and Runx3 loci were lost secondarily.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

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.

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