Abstract

The eh1 motif was detected by its presence in several homeodomain transcription repressors, such as Engrailed and Goosecoid (Logan et al., 1992; Smith and Jayne, 1996; Jimenez et al., 1999). The motif has the consensus sequence FxIxxIL, where only F is completely conserved, and it allows for the recruitment of the corepressor Groucho/TLE (Jimenez et al., 1997, 1992). The structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 protein, together with analysis of the effect of mutants in C. elegans Groucho/TLE homologue UNC-37 suggests an induced fit mechanism for the binding of the eh1 motif to the WD40 domain of Groucho/TLE (Pickles et al., 1992). The Groucho/TLE corepressor proteins repress transcription by recruiting histione deacetylases, and possibly by additional mechanisms (Chen and Courey, 2000).



Subsequently paired box protein Pax5 (Eberhard et al., 2000) and hairless (Barolo et al., 2002; Nagel et al., 2005) have been shown to bind Groucho/TLE through eh1 motifs. [Note that eh1 was termed octapeptide motif in Pax.]



More recently Copley (2005) undertook a bioinformatics survey and identified significantly conserved eh1 motifs in other transcription factor families including forkhead, T-box, zinc finger and doublesex. However, it should be noted that all paired box (plus hairless and one T-box protein, brachyury) motifs consistently substitute the conserved Phe with Tyr or His: the meaning of the implied change of function remains to be elucidated since both variants bind Groucho/TLE.



The transcription factor Dorsal is reported to contain an eh1-like motif reported to be responsible for the recruitment of Groucho but it does not match the other motifs [11311166].



Other Groucho binders in ELM: LIG_WRPW_1, LIG_WRPW_2



Remarkably both eh1 and WRPW bind to the same site on Groucho, across the central hole of the WD40 propeller (Jennings et al., 2006) despite their different sequences and bound conformations. The binding will be mutually exclusive, but it is not known if this is meaningful in practice.