Biology Reference
In-Depth Information
similarly to the mammalian or avian TR. Unfortunately, there are only a
very limited number of studies on gene repression by liganded TR
(
Santos, Fairall, & Schwabe, 2011
). Thus, most discussions have been fo-
cused on the mechanism for T
3
-response genes induced by T
3
(
Grimaldi,
Buisine, Miller, Shi, & Sachs, 2012
)
.
For these genes, in absence of hormone,
TR binds T
3
RE and recruits corepressor complexes carrying chromatin
modification activity that leads to a closed chromatin conformation, inacces-
sible for the transcriptional machinery. T
3
-binding induces a conformational
change of TR that will lead first, to the release of the corepressor complexes
and second, to the recruitment of coactivator complexes carrying a different
set of chromatin modification enzymes. Their actions lead to chromatin
opening favorable to transcription activation.
The expression profiles (
Yaoita & Brown, 1990
), together with the abil-
ity of TR to both repress and activate T
3
-inducible genes in the absence and
presence of TH (
Sachs & Shi, 2000
), respectively, suggest dual functions for
TRs during development (
Sachs et al., 2000
). TR
a
and TR
b
mRNA are
present at very low levels during embryogenesis where their function has
started to be addressed (
Havis et al., 2006
). Next, high levels of TR
a
mRNA
are present after larval hatching and increase to reach a maximum during
metamorphosis. TR
b
mRNA levels are barely detectable before metamor-
phosis, when they will increase in parallel with endogenous T
3
level, again
reaching a peak at the climax. After metamorphosis, the levels of both TR
isoforms decrease to stay low in the juvenile and the adult. The same profiles
were observed analyzing protein levels (
Eliceiri & Brown, 1994
). The tissue
distribution of TR has shown to be correlated with organ transformation
(
Eliceiri & Brown, 1994; Fairclough & Tata, 1997; Kawahara, Baker, &
Tata, 1991
). Thus, in premetamorphic tadpoles, TRs, mostly TR
a
, act to
repress T
3
-response genes. As many of these genes are likely to participate
in metamorphosis, their repression by unliganded TRwill help prevent pre-
mature metamorphosis and ensure a proper period of tadpole growth. TH
synthesis and secretion into the plasma transforms TRs from repressors to
activators, which will induce the expression of TH response genes leading
to metamorphosis.
Analysis of TH action in amphibian metamorphosis will provide a pow-
erful tool to understand the diversity of biological activities known for TH
and the mechanisms that lead to this diversity. Studies in the past two decades
using subtractive hybridization or DNA array have identified many T
3
-
response genes during amphibian metamorphosis (
Brown et al., 1996;
Buchholz, Heimeier, Das, Washington, & Shi, 2007; Buckbinder &
