HMG Domain Proteins

Abstract As described in Chapter 3, transcriptional regulators containing an HMG-type DNA-binding domain appear to function as architectural factors whose primary function is to bend DNA. The HMG domain is an 80-amino-acid motif that was first identified in the High Mobility group nuclear proteins HMGl and HMG2 and the RNA Pol I transcription factor UBF (Jantzen et al., 1990), which bind to DNA in a non-sequence specific manner. The HMG domain has subsequently been shown to de fine a large superfamily of DNA-binding proteins containing over 100 members from eukaryotic species that include yeast, plants, and animals spanning one billion years of evolutionary time (Grosschedl et al., 1994; Laudet et al., 1993). Phylogenetic analysis identified two large subfami lies consisting of sequence-specific DNA binding proteins containing a single HMG domain and non-sequence-specific DNA-binding proteins containing multiple HMG domains (Laudet et al., 1993). All of the se quence-specific HMG-domain proteins that have been analyzed bind to DNA in the minor groove and recognize the consensus sequence 5’-(A/ T)(A/T)CAA(A/T)G-3’ (reviewed by Pevny and Lovell-Badge, 1997). In this chapter, SRY and SOX9, two HMG domain-containing proteins that bind to DNA in a sequence-specific manner and are essential for normal testicular determination and differentiation, will be described.