|
 |
|
EMBO reports 4, 9, 883–888 (2003)
doi:10.1038/sj.embor.embor908
AOP Published online: 15 August 2003
Metamorphic T3-response genes have specific co-regulator requirements
Emmanuelle Havis1, 2, Laurent M. Sachs1, 2 & Barbara A. Demeneix1
|
|
|
|
1 Département Régulations,
Développement et Diversité Moléculaire, USM 501
Muséum National d'Histoire Naturelle, UMR-5166 CNRS, 7 Rue Cuvier,
75231 Paris Cedex 05, France
2 These authors contributed equally to this work
To whom correspondence should be addressed
Laurent M. Sachs Tel: +33 1 40 79 36 04; Fax: +33 1 40 79 36 18;
sachs@mnhn.fr
Received 3 February 2003; Accepted 26 June 2003; Published online 15 August 2003.
|
|
|
|
Abstract
Thyroid hormone receptors (TRs) have several regulatory functions in
vertebrates. In the absence of thyroid hormone (T3;
triiodothyronine), apo-TRs associate with co-repressors to repress
transcription, whereas in the presence of T3, holo-TRs engage
transcriptional coactivators. Although many studies have addressed the
molecular mechanisms of T3 action, it is not known how specific
physiological responses arise. We used T3-dependent amphibian
metamorphosis to analyse how TRs interact with particular co-regulators to
differentially regulate gene expression during development. Using chromatin
immunoprecipitation to study tissue from pre-metamorphic tad-poles, we found
that TRs are physically associated with T3-responsive promoters,
whether or not T3 is present. Addition of T3 results in
histone H4 acetylation specifically on T3-response genes. Most
importantly, we show that individual T3-response genes have distinct
co-regulator requirements, the T3-dependent
co-repressor-to-coactivator switch being gene-specific for both co-regulator
categories.
EMBO reports 4, 9, 883–888 (2003)
doi:10.1038/sj.embor.embor908
AOP Published online: 15 August 2003
|
|
|
|
Introduction
The nuclear receptor superfamily, which includes the thyroid hormone
receptors (TRs), which are encoded by the TRa (NR1A1; Nuclear Receptors Nomenclature Committee, 1999) and
TRb (NR1A2) loci, affects vertebrate development, cell homeostasis and
physiology. TRs bind as heterodimers with 9-cis-retinoic-acid receptor
(RXR) to target genes through cis-acting DNA sequences known as
T3 (thyroid hormone; triiodothyronine)-response elements
(T3REs). In the absence of T3, apo-TRs repress basal
transcription; in the presence of T3, holo-TRs relieve repression
and activate transcription. The repression-to-activation switch involves
changes in co-repressor to coactivator complexes, which are partnered by apo-TR
and holo-TR, respectively (Glass & Rosenfeld,
2000). Given the diversity among co-regulators, their tissue-specific
distribution and their variable expression levels, it is possible that many
modes of gene regulation by TRs could involve different combinations of
co-regulators on particular gene subsets or in specific physiological
contexts.
We used amphibian metamorphosis to investigate TR action in a
physiological context. Metamorphosis is controlled by T3 (Tata, 1993). As in mammals, both TR- and TR-
exist in amphibians such as Xenopus laevis (Yaoita
et al., 1990). The TRb gene is expressed at low levels
before metamorphosis, and is upregulated by T3 during metamorphosis
as a T3 direct-response gene (Ranjan et
al., 1994). By contrast, TR- is activated after completion
of embryogenesis, but well before the production of endogenous T3. A
working model of T3-dependent gene regulation during
pre-metamorphosis is that apo-TRs repress the T3 direct-response
genes and, later, the combination of T3 and TRs permits the
activation of T3 direct-response genes, thus inducing metamorphosis
(Sachs & Shi, 2000).
We used chromatin immunoprecipitation (ChIP) to analyse histone H4
acetylation and recruitment of TR and co-regulators on
T3-response-gene promoters. We focused on four well-characterized
co-regulators that are required for TR action (Glass &
Rosenfeld, 2000): the nuclear co-repressor NCoR, the histone
deacetylase (HDAC) Rpd3, steroid receptor coactivator 3 (SRC3), and the
coactivator p300. Four important results were obtained: first, we demonstrated
constitutive TR binding to T3 direct-response gene promoters in
vivo in pre-metamorphic tadpoles; second, we showed that there is induction
by T3 treatment of histone H4 acetylation on T3-response
gene promoters; third, we showed that there is gene-specific recruitment of
co-regulators at T3-response gene promoters; and finally, we showed
that there is a gene-specific switch from co-repressor to coactivator
recruitment after treatment with T3.
Results
Constitutive TR binding on T3-response-gene
promoters
We first analysed the expression patterns of several control and
T3-response genes in tadpole tails after T3 treatment
(for 48 h). We chose tail tissue because it is the best-characterized organ
that undergoes extensive remodelling during metamorphosis, disappearing
completely due to apoptosis and showing strong upregulation of
T3-response genes. The tail is composed of connective tissue, blood
vessels, spinal cord, notochord and muscles. As skeletal muscle predominates,
it provides a relatively homogeneous tissue for studying specific changes in
gene regulation and chromatin remodelling. Treatment with T3 for 48
h was carried out to mimic the physiological conditions of metamorphosis as
closely as possible and to obtain maximum activation of T3
direct-response genes (Furlow & Brown, 1999).
Total RNA was extracted from tail tissue and used for RT–PCR (PCR after
reverse transcription) analysis. TRa was selected as the only TR gene
that is expressed at all tadpole stages; TRb and TH/bZIP (a basic
leucine-zipper TH-response gene) are the only two Xenopus T3
direct-response genes with sequenced and characterized promoters. MyoD
was chosen because it is a muscle-cell-specific gene. Intestinal fatty acid
binding protein (IFABP) is an intestinal epithelial-cell-specific
gene. IFABP provided a good negative control for these experiments, as
it is not expressed in the tail. Finally, elongation factor 1a
(EF1a) and ribosomal protein L8 (Rpl8) were used as
controls, as they are housekeeping genes. T3 treatment significantly
increased the messenger RNA levels of TRb, TH/bZIP and
MyoD (Fig. 1A), but did not affect the levels of
TRa, EF1a or Rpl8. As expected, IFABP was not
expressed (Fig. 1A). These expression patterns are
consistent with earlier data that were based on northern blots (Wang & Brown, 1993) and RNase protection assays
(Kawahara et al., 1991). Our results
provide the first evidence that MyoD is a T3-response gene in
Xenopus tadpoles.
|
|
Figure 1
Effects of T3 on transcription and DNA binding by thyroid
hormone receptor at T3-response genes in pre-metamorphic stage NF55
tadpole tail. (A) T3 induces transcription of
T3-response genes. Tadpoles were treated for 48 h with 10 nM
T3. Total RNA was extracted from tail tissue and used for
RT–PCR (PCR after reverse transcription) analysis of thyroid hormone
receptor b (TRb), TH/bZIP (a basic leucine-zipper TH-response
gene), MyoD, intestinal fatty acid binding protein
(IFABP), elongation factor 1a (EF1a) and ribosomal
protein L8 (Rpl8) expression. The internal control was Rpl8.
The results were also quantified by phosphoimager scanning. The average values
 s.e.m. of three independent experiments are expressed as multiples of
induction, where 1 is equal to expression in the absence of T3
(control level). For each sample, densitometry readings were normalized against
the value for Rpl8 RNA (except for the Rpl8 data, which were not
normalized). Statistical significance as compared with untreated animals is
indicated as NS (not significant), * (p < 0.05) or
*** (p < 0.001). (B) T3
does not affect TR binding to T3 response elements. Chromatin
isolated from tails of T3-treated tadpoles (10 nM T3 for
48 h) was immunoprecipitated (IP) with antibodies against TR and analysed by
PCR. Aliquots of the chromatin taken before immunoprecipitation were used
directly for PCR as a control (input). For TRb promoters, we
distinguished two sequences containing T3REs (sequence 1 at position
+266 and sequence 2 at positions -800 to -500). All experiments
were carried out at least three times. T3, thyroid hormone
(triiodothyronine).
|
|
|
To obtain direct information about whether these
T3-induced changes in gene expression correlate with the binding of
TR to chromatin, we analysed TR binding in vivo to the promoters of
TRb, TH/bZIP, MyoD, IFABP and EF1a using
ChIP assays. Antibodies that recognize both TR- and TR- were used
to immunoprecipitate formaldehyde-crosslinked, fragmented chromatin from nuclei
that were isolated from tadpole tails and either treated with T3 or
left untreated. The TR-bound DNA fragments were then analysed by
semi-quantitative PCR (Fig. 1B). Primers flanking the
T3REs were used for the TRb and TH/bZIP promoters. For
the TRb promoter, we distinguished two T3RE-containing
sequences ('promoter region 1', which has one T3RE at position +266,
and 'promoter region 2', which has three putative T3REs between
positions -800 and -500; Urnov & Wolffe,
2001). Primers corresponding to the 300 bp immediately upstream of
the transcription start site were used for the MyoDa promoter (Leibham et al., 1994). This promoter has never been
studied for regulation by T3. However, sequence analysis revealed
two imperfect putative T3REs (data not shown). Finally, for the
EF1a promoter (Johnson & Krieg, 1995)
and the IFABP promoter (Gao et al.,
1998), which are not regulated by T3, we chose primers in
the 500-bp region upstream of the transcription start site. As shown in
Fig. 1B, TR was constitutively present on the TRb,
TH/bZIP and MyoD promoters, but was absent from
T3-insensitive promoters (EF1a and IFABP).
Furthermore, T3 does not have any effect on TR binding (Fig. 1B). These results indicate that, first, as previously
described (Sachs & Shi, 2000), apo-TR and
holo-TR bind T3REs in chromatin in vivo, and second, that TR
binds in vivo to both of the T3RE-containing sequences in the
TRb promoter. Moreover, our results highlight the fact that the levels
of TR occupancy correlate with the levels of gene expression. Finally, the
presence of TR on the MyoD promoter suggests that MyoD might be a
T3 direct-response gene. However, more data will be necessary to
confirm this.
Histone acetylation correlates with gene
regulation
We next investigated histone acetylation of promoters. Co-repressor
complexes have HDAC activity, and many coactivators have intrinsic histone
acetyl transferase (HAT) activity, which suggests that TRs might regulate
transcription by modification of local histone acetylation levels (Wolffe,
1997). As shown in Fig. 2, using a ChIP assay
with an antibody specific to acetylated histone H4 (AcH4), we showed that
histone H4 acetylation increased on TRb promoter regions 1 and 2 and on
the TH/bZIP and MyoD promoters, but not on the EF1a and
IFABP promoters. Comparison of Fig. 1A with
Fig. 2 shows that the levels of histone H4 acetylation
correlate with the levels of gene expression. As a control for the specificity
of local histone acetylation, we analysed the acetylation levels of the
MyoD, EF1a and IFABP promoters in intestine. As expected,
as MyoD is not expressed in intestine, its promoter chromatin did not
contain AcH4 (Fig. 2). However, given that IFABP
and EF1a are highly expressed in this tissue, it was not surprising to
find that chromatin from their promoters contained AcH4 (Fig.
2). Finally, for TRb, which is strongly repressed in the absence
of T3, AcH4 was detected at region 2 of the TRb promoter in
the absence of T3, whereas there was no detectable AcH4 at region 1
(Fig. 2, compare TRb lanes 1 and 2). However, both
regions contained AcH4 when T3 was present.
|
|
Figure 2
T3 treatment increases histone H4 acetylation
specifically at the T3-response elements of T3-response
genes in pre-metamorphic tadpoles. Chromatin isolated from tail or intestine of
T3-treated stage NF55 tadpoles (treated with 10 nM T3 for
48 h) was immunoprecipitated (IP) with antibodies against acetylated histone H4
(AcH4) and analysed by PCR, as described for Fig. 1. Each
experiment was carried out at least twice. EF1a, elongation factor
1a; IFABP, intestinal fatty acid binding protein;
T3, thyroid hormone (triiodothyronine); TH/bZIP, a basic
leucine-zipper Th-response gene; TRb, thyroid hormone receptor
b.
|
|
|
Co-repressor recruitment to T3-response-gene
promoters
Apo-TR is known to interact with co-repressor complexes containing
HDAC, whereas holo-TR is known to interact with coactivator complexes
containing HATs. We examined the recruitment and T3-dependent
release of two co-repressors, NCoR (Sachs et al.,
2002) and Rpd3 (Wong et al.,
1998). After confirming that NCoR and Rpd3 are expressed in tail
(Fig. 3A), a ChIP assay was performed using polyclonal
antibodies to Rpd3, the only characterized Xenopus HDAC (Wong et al., 1998), and to Xenopus NCoR, a
co-repressor that seems to function through mechanisms involving HDACs. As
shown in Fig. 3B, Rpd3 is recruited to the TRb
promoter (regions 1 and 2) in a T3-independent manner. However, Rpd3
is recruited to the TH/bZIP promoter only in the absence of
T3 (Fig. 3B), and is never recruited to the
MyoD, EF1a and IFABP promoters (Fig.
3B). We found that NCoR recruitment to the TRb (regions 1 and 2),
TH/bZIP and MyoD promoters decreased after T3
treatment (Fig. 3B). Noticeably, NCoR is never present on
the EF1a and IFABP promoters (Fig. 3B).
Thus, all the T3-response genes that were studied recruit NCoR only
in the absence of T3. By contrast, the recruitment of Rpd3 is
gene-specific, and is not always affected by T3 treatment.
|
|
Figure 3
Effects of T3 on Rpd3 and NCoR co-repressor expression
and recruitment on T3-response elements of T3-response
genes in pre–metamorphic tadpoles. (A) Rpd3 and NCoR protein
levels in tail nuclei are not affected by T3 treatment. Western blot
analysis of protein extracts from the tail nuclei of tadpoles treated with 10
nM T3 for 48 h. (B) Chromatin isolated from tails of
T3-treated tadpoles (treated with 10 nM T3 for 48 h) was
immunoprecipitated (IP) with antibodies against Rpd3 or NCoR and analysed by
PCR, as described for Fig. 1. Pre-immune serum (Pre-I)
was used as a control for antibody specificity. The data represent one of
several independent experiments with identical results. EF1a,
elongation factor 1a; IFABP, intestinal fatty acid binding
protein; NCoR, nuclear co-repressor; T3, thyroid hormone
(triiodothyronine); TH/bZIP, a basic leucine-zipper Th-response gene;
TRb, thyroid hormone receptor b.
|
|
|
Coactivator recruitment to T3-response-gene
promoters
Finally, we examined, in tadpole tail, the effects of T3
on the recruitment of the TR receptor coactivators SRC3 (Kim
et al., 1998) and p300 (Fujii et al.,
1998), which have HAT activity. After verifying that these
coactivator proteins are expressed in the tail at significant levels (Fig.
4A), we analysed whether they were present on the promoters of the genes
studied. Three different situations were found: SRC3 and p300 are continually
present on the promoter of TRb (regions 1 and 2); these coactivators are
only present on TH/bZIP and MyoD promoters if T3 is
present. In the case of the EF1a and IFABP promoters, these
coactivators are never present (Fig. 4B).
|
|
Figure 4
Effects of T3 on steroid receptor coactivator 3 and p300
coactivator expression and recruitment on T3-response elements of
T3-response genes in pre-metamorphic tadpoles. (A) Steroid
receptor coactivator 3 (SRC3) and p300 protein levels in tail nuclei are not
affected by T3 treatment. Western blot analysis of protein extracts
fron tail nuclei of tadpoles treated with 10 nM T3 for 48 h.
(B) Chromatin isolated from tails of T3-treated tadpoles
(treated with 10 nM T3 for 48 h) was immunoprecipitated (IP) with
antibodies against SRC3 or p300 and analysed by PCR, as described for
Fig. 1. Pre-immune serum (Pre-I) was used as a control
for antibody specificity. All experiments were carried out at least three
times. EF1a, elongation factor 1a; IFABP, intestinal
fatty acid binding protein; T3, thyroid hormone
(triiodothyronine); TH/bZIP, a basic leucine-zipper Th-response gene;
TRb, thyroid hormone receptor b.
|
|
|
Discussion
We exploited the absolute dependence of amphibian metamorphosis on
T3 and TRs to analyse successive stages of TR/co-regulator
association during a physiologically defined sequence of events.
Recruitment of NCoR with and without Rpd3
The first model of transcriptional repression by apo-TR, proposed by
Wolffe (1997), described the recruitment of a
multiprotein complex that included NCoR and Rpd3. Recently, on the basis of
results from the TR regulation of the Xenopus TRb promoter, this model
was refined to conclude that apo-TR specifically recruits an NCoR–HDAC3
complex, and not an NCoR–Rpd3 complex (Li et
al., 2002a). Nevertheless, Rpd3 is constitutively associated with
chromatin and contributes to chromatin deacetylation in a non-targeted manner
(Li et al., 2002a). Here, by examining
three T3-response-gene promoters, we show that NCoR is present at
all promoters in the absence of T3, but that NCoR is absent from the
same promoters after T3 treatment. However, Rpd3 recruitment is
gene-specific. Rpd3 is associated with the TRb promoter whether
T3 is present or not, thus confirming the finding of
Li and collaborators (2002a). However, Rpd3 is
recruited to the TH/bZIP promoter only in the absence of T3,
and is never recruited to the MyoD promoter. However, we did observe the
presence of NCoR and Rpd3 on the TH/bZIP promoter, showing that such
complexes can be recruited by apo-TR. Thus, it is still possible that
NCoR–Rpd3 or NCoR–HDAC3 might function through targeting to
different T3 direct-response gene promoters.
Ligand-dependent co-repressor to coactivator
switches
It is thought at present that TRs repress transcription by
recruiting co-repressors and activate transcription by recruiting coactivators.
Our results from the TH/bZIP and MyoD promoters are consistent
with this model. By contrast, at the TRb promoter, Rpd3, SCR3 and p300
are present simultaneously both in the presence and absence of T3,
emphasizing that NCoR release is a key event in the activation of TRb
transcription. This finding supports an earlier hypothesis that TRb
expression results from the relief of repression, rather than from activation
by holo-TR (Collingwood et al., 1999).
The direct interaction of coactivators and co-repressors in a single
regulatory unit has been described before. Examples of these are NCoR and SRC3
(Li et al., 2002b), and NCoR and CBP/p300
(Saleh et al., 2000). Direct interactions
such as these provide an integral control mechanism that affects the timing of
repression and activation. Indeed, the induction of TRb expression
precedes TH/bZIP expression (Furlow & Brown,
1999). These more rapid kinetics could be due to the simultaneous
association of co-repressors and coactivators on the TRb promoter. In
such a complex, the presence of co-repressors inhibits transcription, and their
release rapidly activates transcription. In this context, it would be
interesting to compare the occupancy of the various promoters at various times
after T3 treatment. However, when using an in vivo approach,
one has to take into account the fact that all the cells are not simultaneously
T3 responsive.
A growing body of evidence suggests that co-regulators are
themselves highly regulated by covalent modification. Such modifications not
only alter protein function, but can also confer specificity to ubiquitous
factors. The acetylation of SRC3 by p300 has been shown to induce its release
from the holo-ER form of the oestrogen receptor to attenuate transcriptional
activation by oestradiol (Chen et al.,
1999). In addition, covalent modification of CBP/p300 induces changes
in HAT activity, substrate specificity, protein–protein interactions and
stability (Gamble & Freedman, 2002). For
example, on binding of NCoR and CBP to the homeobox heterodimer pbx–hox,
protein kinase A stimulation of CBP has been found to facilitate the switch
from transcriptional repression to activation in this system (Saleh et al., 2000).
Transcriptional activation might also involve chromatin structure.
Binding by apo-TR to the TRb promoter T3RE is potentiated by
assembly of the DNA into a mature array of transitionally positioned
nucleosomes, and holo-TR disrupts this array, creating a lower-affinity
template for itself (Urnov & Wolffe, 2001).
Another possibility is the recruitment of other types of coactivator complexes
by T3 treatment. Indeed, TR can recruit SRC–p300 and Mediator
complexes in at least two sequential steps. SRC and p300 are recruited first
and rapidly induce histone acetylation, followed by the recruitment of the
Mediator complex (Sharma & Fondell, 2002).
However, sequential models are usually cyclic, with windows of time in the
range of minutes (Shang et al. 2000;
Sharma & Fondell, 2002), and these complexes
are all required for correct gene transcription (Huang et
al., 2003).
Our results suggest that during metamorphosis, combinatorial
associations of TR, co-repressor and/or coactivator molecules that are
influenced by cell history and promoter context provide the specificity of the
response of genes to T3. This study underlines the importance of
tissue specificity with regard to promoter occupancy. We are now analysing this
problem in tissues such as intestine and brain that show different metamorphic
organizational responses to those of tail tissue. Finally, promoter specificity
for co-regulator requirements is a particularly interesting phenomenon, as the
different gene regulatory mechanisms revealed in this study might be correlated
with the multiple T3-induced cellular responses that underlie tissue
remodelling during metamorphosis.
Methods
Animals.
Xenopus laevis tadpoles were staged in accordance with the
method of Nieuwkopp & Faber (NF staging;
1956). For T3 treatment, stage NF55 tadpoles were kept for
48 h in 5 l of dechlorinated tap water with 10 nM 3,5,3' triiodothyronine
(T3; Sigma). Tadpoles were sacrificed by decapitation after
anaesthesia. Animal care was carried out in accordance with institutional
guidelines.
RT–PCR.
Tissues were stored at 4 °C in RNAlater (Ambion). RNA
extractions and RT–PCR were carried out as described in
Sachs et al. (2002). The primers used are
shown in Table 1. To define for each gene the optimal
number of PCR cycles for quantitative analysis, 10–24 cycles were carried
out (data not shown). The numbers of cycles chosen were as follows:
EF1a, 14 cycles; TH/bZIP, 18 cycles; TRa and MyoD,
20 cycles; TRb and IFABP, 22 cycles. PCR products were loaded
onto acrylamide gels (6%) in 1  TBE buffer and visualized by
autoradiography. Phosphoimager scanning (Molecular Dynamics) was used to
quantify each of the PCR products. A Student's t-test was used to assess
statistical differences between means.
|
|
|
|
|
Antibodies.
Rabbit polyclonal antibodies against Xenopus Rpd3 and
Xenopus NCoR have been described previously (Vermaak
et al., 1999; Sachs et al.,
2002). Rabbit polyclonal antibodies against Xenopus SRC3 were
generated against two synthetic peptides (amino acids 1–20,
MSGLGENSLDPLASETRKRK, and amino acids 62–77, DNFNVKPDKCAILKETVR) and
those against Xenopus p300 were generated against two synthetic peptides
(amino acids 1033–1049, KSEPVELEEKKEEVKTE, and amino acids
1487–1506, KPRLQEWYKKMLDKSVSER).
ChIP assays.
ChIP assays were carried out as described by Sachs & Shi (2000). 5  l of anti-AcH4 antiserum
(Upstate Biotechnology) or 8 l of antibodies against the Xenopus
proteins TR, Rpd3, NCoR, p300 and SRC3 were used for immunoprecipitation.
Pre-immune serum was used as a control for antibody specificity.
Immunoprecipitated DNA was analysed by semi-quantitative PCR, as described in
Sachs & Shi (2000). The primers used are shown
in Table 1. 10 l of PCR product was resolved on a
6% acrylamide–TBE gel, and bands were visualized by autoradiography.
Protein isolation and western blotting.
After the isolation of tail nuclei (Sachs &
Shi, 2000), protein extraction and western blotting were carried out
as described in Sachs et al. (2001). One
modification to this method was the time of transfer to nitrocellulose
membranes (Bio-Rad), which was 1 h for Rpd3 and SRC3 and overnight for NCoR and
p300.
|
|
Acknowledgements
We thank G. Benisti, J.-P. Chaumeil and E. LeGoff for animal care. The
Association Pour la Recherche Contre le Cancer, the CNRS and the Muséum
National d'Histoire Naturelle supported this work.
|
|
References
Chen, H., Lin, R.J., Schiltz, R.L., Chakravarti, D., Nash, A., Nagy, L., Privalsky, M.L., Nakatani, Y. & Evans, R.M. ( 1999) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 90, 569–580.
Collingwood, T.N., Urnov, F.D. & Wolffe, A.P. ( 1999) Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription. J. Mol. Endocrinol., 23, 255–275. | ChemPort |
Fujii, G., Tsuchiya, R., Itoh, Y., Tashiro, K. & Hirohashi, S. ( 1998) Molecular cloning and expression of Xenopus p300/CBP. Biochim. Biophys. Acta, 1443, 41–54. | Article | PubMed | ISI | ChemPort |
Furlow, J.D. & Brown, D.D. ( 1999) In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis. Mol. Endocrinol., 13, 2076–2089. | PubMed | ISI | ChemPort |
Gamble, M.J. & Freedman, L.P. ( 2002) A coactivator code for transcription. Trends Biochem. Sci., 27, 165–167. | Article | PubMed | ISI | ChemPort |
Gao, X., Sedgwick, T., Shi, Y.-B. & Evans, T. ( 1998) Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation. Mol. Cell. Biol., 18, 2901–2911. | PubMed | ISI | ChemPort |
Glass, C.K. & Rosenfeld, M.G. ( 2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev., 14, 121–141. | PubMed | ISI | ChemPort |
Huang, Z.-Q., Li, J., Sachs, L.M., Cole, P.A. & Wong, J. ( 2003) A role for cofactor–cofactor and cofactor–histone interactions in targeting p300, SWI:SNF and Mediator for transcription. EMBO J., 22, 2146–2155. | Article | PubMed | ISI | ChemPort |
Johnson, A.D. & Krieg, P.A. ( 1995) A Xenopus laevis gene encoding EF-1S, the somatic form of elongation factor 1: sequence, structure, and identification of regulatory elements required for embryonic transcription. Dev. Genet., 17, 280–290. | PubMed | ISI | ChemPort |
Kawahara, A., Baker, B.S. & Tata, J.R. ( 1991) Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis. Development, 112, 933–943. | PubMed | ISI | ChemPort |
Kim, H.J., Lee, S.K., Na, S.Y., Choi, H.S. & Lee, J.W. ( 1998) Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2. Mol. Endocrinol., 12, 1038–1047. | PubMed | ISI | ChemPort |
Leibham, D., Wong, M.-W., Cheng, T.-C., Schroeder, S., Weil, P.A., Olson, E.N. & Perry, M. ( 1994) Binding of TFIID and MEF2 to the TATA element activates transcription of the Xenopus MyoDa promoter. Mol. Cell. Biol., 14, 686–699. | PubMed | ISI | ChemPort |
Li, J., Lin, Q., Wang, W., Wade, P. & Wong, J. ( 2002a) Specific targeting and constitutive association of histone deacetylase complexes during transcriptional repression. Genes Dev., 16, 687–692. | ISI | ChemPort |
Li, X., Kimbrel, E.A., Kenan, D.J. & McDonnel, D.P. ( 2002b) Direct interactions between corepressors and coactivators permit the integration of nuclear receptor-mediated repression and activation. Mol. Endocrinol., 16, 1482–1891. | ISI | ChemPort |
Nieuwkoop, P. & Faber, J. ( 1956) Normal table of Xenopus laevis. North Holland, Amsterdam, The Netherlands.
Nuclear Receptors Nomenclature Committee ( 1999) A unified nomenclature system for the nuclear receptor superfamily. Cell, 97, 161–163. | PubMed | ISI |
Ranjan, M., Wong, J. & Shi, Y.-B. ( 1994) Transcriptional repression of Xenopus TR gene is mediated by a thyroid hormone response element located near the start site. J. Biol. Chem., 269, 24699–24705. | PubMed | ISI | ChemPort |
Sachs, L.M. & Shi, Y.-B. ( 2000) Targeted chromatin binding and histone acetylation in vivo by thyroid hormone receptor during amphibian development. Proc. Natl Acad. Sci. USA, 97, 13138–13143. | Article | PubMed | ChemPort |
Sachs, L.M., Amano, T. & Shi, Y.-B. ( 2001) An essential role of histone deacetylases in postembryonic organ transformations in Xenopus laevis. Int. J. Mol. Med., 8, 595–601. | PubMed | ISI | ChemPort |
Sachs, L.M., Jones, P.L., Havis, E., Rouse, N., Demeneix, B.A. & Shi, Y.-B. ( 2002) Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development. Mol. Cell. Biol., 22, 8527–8538. | Article | PubMed | ISI | ChemPort |
Saleh, M., Rambaldi, I., Yang, X.-J. & Featherstone, M. ( 2000) Cell signaling switches HOX–PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases. Mol. Cell. Biol., 20, 8623–8633. | Article | PubMed | ISI | ChemPort |
Shang, Y., Hu, X., DiRenzo, J., Lazar, M.A. & Brown, M. ( 2000) Cofactor dynamics and sufficiency in oestrogen receptor-regulated transcription. Cell, 103, 843–852. | PubMed | ISI | ChemPort |
Sharma, D. & Fondell, J.D. ( 2002) Ordered recruitment of histone acetyltransferases and TRAP/mediator complex to thyroid hormone-responsive promoters in vivo. Proc. Natl Acad. Sci. USA, 99, 7934–7939. | Article | ChemPort |
Tata, J.R. ( 1993) Gene expression during metamorphosis: an ideal model for post-embryonic development. Bioessays, 15, 239–248. | PubMed | ISI | ChemPort |
Urnov, F.D. & Wolffe, A.P. ( 2001) An array of positioned nucleosomes potentiates thyroid hormone receptor action in vivo. J. Biol. Chem., 276, 19753–19761. | Article | PubMed | ISI | ChemPort |
Vermaak, D., Wade, P.A., Jones, P.L., Shi, Y.-B. & Wolffe, A.P. ( 1999) Functional analysis of the Sin3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte. Mol. Cell. Biol., 19, 5847–5860. | PubMed | ISI | ChemPort |
Wang, Z. & Brown, D.D. ( 1993) Thyroid hormone-induced gene expression program for amphibian tail resorption. J. Biol. Chem., 268, 16270–16278. | PubMed | ISI | ChemPort |
Wolffe, A.P. ( 1997) Sinful repression. Nature, 387, 16–17. | Article | PubMed | ISI | ChemPort |
Wong, J., Patterton, D., Imhof, A., Guschin, D., Shi, Y.-B. & Wolffe, A.P. ( 1998) Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylase. EMBO J., 17, 520–534. | Article | PubMed | ISI | ChemPort |
Yaoita, Y., Shi, Y.-B. & Brown, D.D. ( 1990) Xenopus laevis and thyroid hormone receptors. Proc. Natl Acad. Sci. USA, 87, 7090–7094. | PubMed | ChemPort |
|
|
top  |
|
|
|
