Ligand-bound nuclear receptors (NRs) recruit cofactors such as members of the p160 family and CREB-binding protein (CBP) to activate transcription. We have cloned the
Xenopus homologue of the human ...transcription intermediary factor 2 (TIF2), a member of the p160 family of cofactors.
Xenopus
TIF2 (
XTIF2) mRNA is expressed homogeneously during late blastula–early gastrula stages and later becomes highly expressed in the notochord. To study the function of
XTIF2 during development, we have used two dominant negative constructs, one encompassing the NR-binding domain and the other the CBP interacting region of XTIF2. Overexpression of the
XTIF2 dominant negative mRNAs causes ectopic expression of
Xenopus
Brachyury (
Xbra) and
MyoD in all tissue layers. Moreover, ectopic expression of the dominant negative construct that contains the CBP-binding region produces strong phenotypes at hatching stage such as loss of head structures, shortened trunks and open blastopores, which can be rescued by
XTIF2 coexpression. These observed defects are due, at least in part, to repression of dorsal mesoderm and endoderm genes. Our data suggest the existence of a NR pathway that requires XTIF2 and CBP to repress
Xbra and
XMyoD.
The
iroquois (
iro) genes encode evolutionary conserved homeoproteins that participate in many developmental processes reviewed in Development 128 (2001) 2847. In
Xenopus, the Iro protein Xiro1 is a ...repressor, required during gastrulation for neural plate formation, that downregulates
Bmp4. During neurulation, Xiro1 participates in the pattering of the neuroectoderm. In this work, we report the cloning and pattern of expression of
XCoREST, another gene repressed by Xiro1. During
Xenopus development,
XCoREST is expressed in territories in which neurogenesis takes place.
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