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2003; Zhang, Kalkum, Chait, & Roeder, 2002; Zhang & Lazar, 2000
). This
leads to local deacetylation of histones H3 and H4 transcriptional inhibition
(
Fig. 10.1
). The binding by TH induces a conformational change in
TR, leading to the release of corepressor complexes and the binding of
coactivator complexes and gene activation. Among the coactivator com-
plexes include those involved in chromatin disruption/remodeling as
well as histonemodifications such as those containing the relatedTR-binding
coactivators SRC-1, 2, and 3, which complex with among other proteins
CBP/p300 and protein arginine methyltransferase 1 (PRMT1) (
Chen
et al., 1997, 1999; Demarest et al., 2002; Heimeier, Hsia, & Shi, 2008;
Huang, Li, Sachs, Cole, & Wong, 2003; Ito & Roeder, 2001; Koh, Chen,
Lee, & Stallcup, 2001; Li, O'Malley, & Wong, 2000; Matsuda, Paul, Choi,
Hasebe, & Shi, 2009; Matsuda, Paul, Choi, & Shi, 2007; Matsuura et al.,
2012; McKenna & O'Malley, 2001; Onate, Tsai, Tsai, & O'Malley, 1995;
Rachez & Freedman, 2001; Sheppard, Harries, Hussain, Bevan, & Heery,
2001; Shi et al., 2012; Torchia et al., 1997; Wong et al., 1995, 1997; Yen,
2001; Zhang & Lazar, 2000
).
As the mediators of the effects of TH (see below), TRs and RXRs are
expected to be present during amphibian metamorphosis. Indeed, their
mRNAs are highly expressed during amphibian metamorphosis. In the
pseudo-tetraploid
X. laevis
, there are two TR
a
and two TR
b
genes. The
TR
a
genes are activated as early as stage 41, shortly after tadpole hatching
at stage 35/36, and reached high levels by stage 45 (
Fig. 10.1
)(
Kanamori
& Brown, 1992; Yaoita & Brown, 1990
), the onset of tadpole feeding
(
Nieuwkoop & Faber, 1956
), and their expression is maintained at high
levels throughout metamorphosis (
Fig. 10.1
). The TR
b
genes have little
expression in premetamorphic tadpoles but are highly activated during
metamorphosis, coinciding with the rise of endogenous TH (
Fig. 10.1
)
(
Kanamori & Brown, 1992; Shi, Yaoita, & Brown, 1992; Wang &
Brown, 1993; Yaoita & Brown, 1990
). Similarly, RXR
a
and RXR
g
are
also expressed in premetamorphic as well as metamorphosing tadpoles
(
Fig. 10.1
)(
Wong & Shi, 1995
). It has been shown that the TR
b
genes
are activated directly by TR via the binding to the promoter region
(
Ranjan, Wong, & Shi, 1994; Shi et al., 1992
), which explains the correla-
tion of the mRNA levels with plasma TH (
Fig. 10.1
). The mechanisms
governing the developmental expression patterns of TR
a
and RXR genes
remain to be determined.
The expression studies led us to propose a dual function model for TR
during the frog development (
Fig. 10.1
)(
Sachs et al., 2000; Shi, Wong,
