The Wilms' tumour suppressor protein WT1 contains a transcriptional regulat
ory domain that can either activate or repress transcription depending upon
its cellular environment. The mechanistic basis for this dichotomy is uncl
ear however. Here, we dissect the transcriptional regulatory domains of WT1
. We find that a region within the domain of WT1 attributed to transcriptio
nal repression is a potent suppressor of the activation domain at several p
romoters and in different cell types. In vitro transcription analysis sugge
sts that the mechanism of suppression of the activation domain occurs at th
e level of transcription initiation. Furthermore we find that the WT1 suppr
ession domain is able to inhibit a heterologous activation domain when fuse
d in cis. Dissection of this domain resulted in the delineation of a 30 ami
no acid region that was sufficient to confer suppression of a transcription
al activation domain both in vivo and in vitro. Additionally, we find that
the WT1 transcriptional activation domain interacts with the general transc
ription factor TFIIB and that this interaction is not affected by the suppr
ession domain. Taken together, these studies suggest that the suppression d
omain of WT1 interacts with a cosuppressor protein to mediate inhibition of
the WT1 transcriptional activation domain.