Biology Reference
In-Depth Information
dnTR expression
Morphological
changes
TH response
gene expresson
Figure 10.2 Dose-dependent inhibition of T3-induced metamorphosis by the expres-
sion of a dnTR. Transgenic tadpoles were generated to overexpress a dnTR with GFP
fused at the N terminus. The premetamorphic tadpoles were treated with T3 to induce
metamorphosis. Note that the degree of inhibition of T3-induced metamorphosis cor-
relates with the level of dnTR overexpression as judged from the GFP expression levels
in the tadpoles (DR Buchholz and Y-B Shi, unpublished). See
Buchholz et al. (2003)
for
more details.
not only necessary but also sufficient to mediate the effects of TH during
Xenopus
metamorphosis.
3. UNLIGANDED TR RECRUITS COREPRESSOR
COMPLEXES TO CONTROL METAMORPHIC TIMING
The dual function model for TR (
Fig. 10.1
) predicts that gene re-
pression by unliganded TR during premetamorphosis is important for
proper tadpole growth and development before undergoing metamorphic
transformations. As summarized above, unliganded TR can recruit core-
pressor to target promoters to repress their expression. Chromatin immu-
nization (ChIP) analyses have shown that during
Xenopus
development,
the TR-binding corepressors N-CoR and SMRT are recruited by TR in
premetamorphic tadpoles to endogenous target genes (
Sachs et al., 2002;
Tomita, Buchholz, & Shi, 2004
). These corepressors are released from the
target promoters during natural metamorphosis or upon TH treatment
of premetamorphic tadpoles. Both N-CoR and SMRT form large com-
plexes containing other proteins such as TBLR1 and HDAC3 (
Guenther
et al., 2000; Ishizuka & Lazar, 2003; Jones et al., 2001; Jones & Shi, 2003;
