FUNCTIONAL-ANALYSIS OF MOUSE HOXA-7 IN SACCHAROMYCES-CEREVISIAE - SEQUENCES OUTSIDE THE HOMEODOMAIN BASE CONTACT ZONE INFLUENCE BINDING ANDACTIVATION

The murine developmental control gene product, Hoxa-7, was shown to fu nction as a DNA-binding transactivator in Saccharomyces cerevisiae. Th e importance of the ATTA core, the preference for antp class flanking nucleotides, the importance of Asn-51 of the homeodomain (HD), and the synergism of multiple binding sites all reflect properties that have previously been described for HOM or Hox proteins in tissue culture sy stems. A comparison of contact positions among genes of paralog groups and classes of mammalian HDs points to a lack of diversity in positio ns that make base contact, suggesting that besides the combination of HD amino acid-base pair contacts, another means of recognizing differe nces between targets must exist if Hox genes select different targets. The HD of antennapedia is identical to the Hoxa-7 HD. The interaction of Hoxa-7 with the exact sequence used in the nuclear magnetic resona nce three-dimensional structural analysis on the antennapedia HD was s tudied. Hoxa-7 binding and transactivation was influenced by sequences outside of the known base contact zone of this site. We conclude that Hoxa-7 protein has a second means to interact with DNA or/and that th e sequences flanking the base contact zone influence HD interactions b y distorting DNA within the contact zone (base or backbone). This resu lt is discussed in terms of DNA flexure and two modes of transcription used in S. cerevisiae.