Mk. Gross et P. Gruss, FUNCTIONAL-ANALYSIS OF MOUSE HOXA-7 IN SACCHAROMYCES-CEREVISIAE - SEQUENCES OUTSIDE THE HOMEODOMAIN BASE CONTACT ZONE INFLUENCE BINDING ANDACTIVATION, Molecular and cellular biology, 14(1), 1994, pp. 238-254
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.