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BMC Genomics 2007 Jun 28;8:201. doi: 10.1186/1471-2164-8-201.
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Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators.

Yaklichkin S , Vekker A , Stayrook S , Lewis M , Kessler DS .

BACKGROUND: The Fox gene family comprises a large and functionally diverse group of forkhead-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. RESULTS: 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 alpha-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction. CONCLUSION: 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.

PubMed ID: 17598915
PMC ID: PMC1939712
Article link: BMC Genomics
Grant support: [+]

Species referenced: Echinodermata
Genes referenced: en1 ephx2 foxc1 foxd4 foxg1 foxq1 irak1bp1 LOC100887844 LOC100890537 LOC115925415 LOC591473 polr3a tle2

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References [+] :
Andrioli, Groucho-dependent repression by sloppy-paired 1 differentially positions anterior pair-rule stripes in the Drosophila embryo. 2005, Pubmed