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The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

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Runx and CBFβ genes in cnidarians and a sponge. A) Schematic representation of the genomic organization of the Runx gene from the sea-anemone Nematostella vectensis. Boxes indicate exons connected by lines representing introns. The Runt domain (RD) is in green. The conserved VWRPY Groucho-binding motif is in yellow. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids) in the Nematostella and Hydra genes. B) Conservation of the RD from sponges and cnidarians to mammals. The arrowhead represents the end of the RD and * marks the cysteine residues which function as 'redox switches". C) Schematic representation of the CBFβ gene from Nematostella vectensis. The red line in the last exon represents the location of the stop codon. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids). D) Conservation of CBFβ from cnidarians to mammals.
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Figure 2: Runx and CBFβ genes in cnidarians and a sponge. A) Schematic representation of the genomic organization of the Runx gene from the sea-anemone Nematostella vectensis. Boxes indicate exons connected by lines representing introns. The Runt domain (RD) is in green. The conserved VWRPY Groucho-binding motif is in yellow. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids) in the Nematostella and Hydra genes. B) Conservation of the RD from sponges and cnidarians to mammals. The arrowhead represents the end of the RD and * marks the cysteine residues which function as 'redox switches". C) Schematic representation of the CBFβ gene from Nematostella vectensis. The red line in the last exon represents the location of the stop codon. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids). D) Conservation of CBFβ from cnidarians to mammals.

Mentions: The Nematostella Runx gene (Nv-Runx) encodes a predicted protein 496 amino acids long. It contains four exons, the first two of which encode the highly conserved Runt domain (RD). Within this domain, the Nematostella sequence is 81% identical and 93% similar to human RUNX1 (Figure 2A, B). The third and fourth exons encoding the C-terminus of the protein do not exhibit sequence similarity to other Runx proteins, nor to any other protein housed in the NCBI GenBank non-redundant database [48]. Nevertheless, as in other Runx proteins, the Nv-Runx C-terminal region, residues 148–495, is enriched in proline (13%), serine (9%) and threonine (8%) residues. The anemone protein ends with the canonical C-terminal VWRPY Groucho binding motif [33]. A characteristic intron at nucleotide position 328 within the RD, conserved amongst protostomes and deuterostomes [7], is also conserved in Nv-Runx. The second RD exon of Nematostella is identical in size to the corresponding exon in all deuterostome Runx genes (105 bp) that have been described. The closest similarity in gene structure is for the echinoderm Runx where the N-terminal part of the RD is encoded by a single exon while in other deuterostomes it spans two exons [7].


The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Runx and CBFβ genes in cnidarians and a sponge. A) Schematic representation of the genomic organization of the Runx gene from the sea-anemone Nematostella vectensis. Boxes indicate exons connected by lines representing introns. The Runt domain (RD) is in green. The conserved VWRPY Groucho-binding motif is in yellow. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids) in the Nematostella and Hydra genes. B) Conservation of the RD from sponges and cnidarians to mammals. The arrowhead represents the end of the RD and * marks the cysteine residues which function as 'redox switches". C) Schematic representation of the CBFβ gene from Nematostella vectensis. The red line in the last exon represents the location of the stop codon. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids). D) Conservation of CBFβ from cnidarians to mammals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2527000&req=5

Figure 2: Runx and CBFβ genes in cnidarians and a sponge. A) Schematic representation of the genomic organization of the Runx gene from the sea-anemone Nematostella vectensis. Boxes indicate exons connected by lines representing introns. The Runt domain (RD) is in green. The conserved VWRPY Groucho-binding motif is in yellow. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids) in the Nematostella and Hydra genes. B) Conservation of the RD from sponges and cnidarians to mammals. The arrowhead represents the end of the RD and * marks the cysteine residues which function as 'redox switches". C) Schematic representation of the CBFβ gene from Nematostella vectensis. The red line in the last exon represents the location of the stop codon. The numbers beneath the diagram represent the sizes of the various exon products (in amino acids). D) Conservation of CBFβ from cnidarians to mammals.
Mentions: The Nematostella Runx gene (Nv-Runx) encodes a predicted protein 496 amino acids long. It contains four exons, the first two of which encode the highly conserved Runt domain (RD). Within this domain, the Nematostella sequence is 81% identical and 93% similar to human RUNX1 (Figure 2A, B). The third and fourth exons encoding the C-terminus of the protein do not exhibit sequence similarity to other Runx proteins, nor to any other protein housed in the NCBI GenBank non-redundant database [48]. Nevertheless, as in other Runx proteins, the Nv-Runx C-terminal region, residues 148–495, is enriched in proline (13%), serine (9%) and threonine (8%) residues. The anemone protein ends with the canonical C-terminal VWRPY Groucho binding motif [33]. A characteristic intron at nucleotide position 328 within the RD, conserved amongst protostomes and deuterostomes [7], is also conserved in Nv-Runx. The second RD exon of Nematostella is identical in size to the corresponding exon in all deuterostome Runx genes (105 bp) that have been described. The closest similarity in gene structure is for the echinoderm Runx where the N-terminal part of the RD is encoded by a single exon while in other deuterostomes it spans two exons [7].

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

Show MeSH
Related in: MedlinePlus