Haplotypes of bovine FoxO1 gene sequence variants and association with growth traits in Qinchuan cattle

The winged helix or forkhead box (Fox) class of transcription factors constitutes a family of structurally related transcriptional activators that have been identified in species ranging from yeast to human. The first member of this transcription factor class was identified as a nuclear homeotic gene involved in embryonic development in Drosophila melanogaster (Weigel et al. 1989). The FoxO family of forkhead transcription factors represents a subfamily within the larger group of Fox transcription factors. Mammalian FoxO proteins (FoxO1, FoxO3a, FoxO4 and FoxO6), which are homologous to Caenorhabditis elegans protein DAF-16, belong to the O (‘other’) class of the Fox superfamily (Kaestner et al. 2000; Barthel et al. 2005). As transcription factors in the nucleus, the primary function of FoxO proteins is to bind to their cognate DNA target sequences as monomers. The cocrystal structure of another Fox protein, HNF-3γ , with DNA shows that there are 14 protein–DNA contacts distributed throughout the forkhead domain, but the third α-helix (H3) plays the most important role in a winged helix/forkhead protein’s DNA-binding specificity (Clark et al. 1993). In addition, both winged loops also make important interactions with DNA (Clark et al. 1993; Boura et al. 2007). Although the molecular basis of the DNA-binding specificity of FoxO transcription factors is poorly understood, high-affinity DNA-binding studies have identified a consensus FoxOrecognized element (FRE), (G/C) (T/A)AA(C/T)AA (Biggs Iii et al. 1999; Furuyama et al. 2000; Gilley et al. 2003).