Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators

<p>Abstract</p> <p>Background</p> <p>The Fox gene family comprises a large and functionally diverse group of <it>forkhead</it>-related transcriptional regulators, many of which are essential for metazoan embryogenesis and physiology. Defining conserved functional domains that mediate the transcriptional activity of Fox proteins will contribute to a comprehensive understanding of the biological function of Fox family genes.</p> <p>Results</p> <p>Systematic analysis of 458 protein sequences of the metazoan Fox family was performed to identify the presence of the engrailed homology-1 motif (eh1), a motif known to mediate physical interaction with transcriptional corepressors of the TLE/Groucho family. Greater than 50% of Fox proteins contain sequences with high similarity to the eh1 motif, including ten of the nineteen Fox subclasses (A, B, C, D, E, G, H, I, L, and Q) and Fox proteins of early divergent species such as marine sponge. The eh1 motif is not detected in Fox proteins of the F, J, K, M, N, O, P, R and S subclasses, or in yeast Fox proteins. The eh1-like motifs are positioned C-terminal to the winged helix DNA-binding domain in all subclasses except for FoxG proteins, which have an N-terminal motif. Two similar eh1-like motifs are found in the zebrafish FoxQ1 and in FoxG proteins of sea urchin and amphioxus. The identification of eh1-like motifs by manual sequence alignment was validated by statistical analyses of the Swiss protein database, confirming a high frequency of occurrence of eh1-like sequences in Fox family proteins. Structural predictions suggest that the majority of identified eh1-like motifs are short α-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction.</p> <p>Conclusion</p> <p>A search for eh1 Groucho interaction motifs in the Fox gene family has identified eh1-like sequences in greater than 50% of Fox proteins. The results predict a physical and functional interaction of TLE/Groucho corepressors with many members of the Fox family of transcriptional regulators. Given the functional importance of the eh1 motif in transcriptional regulation, our annotation of this motif in the Fox gene family will facilitate further study of the diverse transcriptional and regulatory roles of Fox family proteins.</p

The positional distribution of the C-terminal eh1-like motifs in Fox proteins of the B, E, H and Q subclasses (A) and the A D, C and I subclasses (B)

<p><b>Copyright information:</b></p><p>Taken from "Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators"</p><p>http://www.biomedcentral.com/1471-2164/8/201</p><p>BMC Genomics 2007;8():201-201.</p><p>Published online 28 Jun 2007</p><p>PMCID:PMC1939712.</p><p></p> Size of polylinker represents the distance between the first residue of the eh1 motif and the conserved C-terminal residue of the winged helix DNA-binding domain

A phylogenetic tree for proteins of the FoxE subclass and the FoxC and FoxD outgroups

<p><b>Copyright information:</b></p><p>Taken from "Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators"</p><p>http://www.biomedcentral.com/1471-2164/8/201</p><p>BMC Genomics 2007;8():201-201.</p><p>Published online 28 Jun 2007</p><p>PMCID:PMC1939712.</p><p></p> A neighbor-joining method was used to construct the tree topology and bootstrapping values are shown at each branch point (percentage of 1000 bootstrap samples) using the MEGA 3.1 software. Gaps were deleted in pairwise comparisons. The distance scale below the tree represents the number of substitutions per site. The C and D families are collapsed for better illustration. Protein sequences that lack a recognizable eh1-like motif are represented by blue triangles. Proteins and subclasses that contain an eh1-like motif are represented by red circles

The diagrams summarize the amino acid compositions of the eh1-like motifs identified in Fox proteins

<p><b>Copyright information:</b></p><p>Taken from "Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators"</p><p>http://www.biomedcentral.com/1471-2164/8/201</p><p>BMC Genomics 2007;8():201-201.</p><p>Published online 28 Jun 2007</p><p>PMCID:PMC1939712.</p><p></p> The amino acid usage frequency of eh1-like motifs identified in invertebrate (A) and vertebrate (B) Fox proteins. The diagrams were generated with the WebLogo program [44]

Positional fluctuations of eh1-like motifs in the ortholog and paralog groups of vertebrate Fox proteins

<p><b>Copyright information:</b></p><p>Taken from "Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators"</p><p>http://www.biomedcentral.com/1471-2164/8/201</p><p>BMC Genomics 2007;8():201-201.</p><p>Published online 28 Jun 2007</p><p>PMCID:PMC1939712.</p><p></p> (A) Positional fluctuations of the eh1-like motifs of the ortholog and paralog groups of the A, C and D subclasses. (B) Positional fluctuations of the eh1-like motifs of the ortholog and paralog groups of the B, E, H and Q subclasses. Polylinker represents the distance between the first residue of the eh1-like motif and the conserved C-terminal residue of the winged helix DNA-binding domain. The paralog groups within a Fox subclass are indicated on the -axis