OVO controls germline and epidermis differentiation in flies and mice. In t
he Drosophila germline, alternative OVO-B and OVO-A isoforms have a common
DNA-binding domain, but different N-termini, We show that these isoforms ar
e transcription factors with opposite regulatory activities. Using yeast on
e-hybrid assays, we identified a strong activation domain within a common r
egion and a counteracting repression domain within the OVO-Aspecific region
. In flies, OVO-B positively regulated the ovarian tumor promoter, while OV
O-A was a negative regulator of the ovarian turner and eve promoters. OVO-B
isoforms supplied ovo(+) function in the female germline and epidermis, wh
ile OVO-A isoforms had dominant-negative activity in both tissues, Moreover
, elevated expression of OVO-A resulted in maternal-effect lethality while
the absence of OVO-A resulted in maternal-effect sterility. Our data indica
te that tight regulation of antagonistic OVO-B and OVO-A isoforms is critic
al for germline formation and differentiation.