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Previous Article | Next Article 
Molecular and Cellular Biology, August 1999, p. 5486-5494, Vol. 19, No. 8
Institut de Génétique et de
Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch
Cédex, C.U. de Strasbourg, France
Received 9 October 1998/Returned for modification 14 December
1998/Accepted 14 May 1999
We have identified novel interactions between the human
(h)TATA-binding protein-associated factor TAFII55 and the
ligand-binding domains (LBDs) of the nuclear receptors for vitamin
D3 (VDR) and thyroid hormone (TR Transcription factor TFIID is one of
the general factors required for accurate and regulated initiation by
RNA polymerase II. TFIID comprises the TATA-binding protein (TBP) and
TBP-associated factors (TAFIIs) (5, 9, 10, 13, 15, 17,
20, 43, 55). The cDNAs encoding many human (h)TAFIIs
have been isolated, revealing a striking sequence conservation with
yeast and Drosophila TAFIIs (14, 21, 22,
28-30).
The TAFII proteins are of particular interest, since they
play several roles in transcriptional regulation, some of them being present not only in TFIID but also in the SAGA, PCAF, and TFTC complexes (18, 25, 35, 50). TAFIIs contribute to
promoter recognition both directly by interaction of specific
TAFIIs with promoter sequences (46, 47) and more
generally through multiple TAFII-DNA interactions which
possibly arise from the wrapping of DNA around a nucleosome-like
structure formed by TAFIIs with histone fold motifs
(6, 34, 35).
An increasing body of results also shows that hTAFII28,
hTAFII135, and hTAFII105 can act as specific
transcriptional coactivators in mammalian cells. For example, distinct
domains of hTAFII135 interact specifically with Sp1, cyclic
AMP response element-binding protein, and E1A and coexpression of the
fragments of TAFII135 with which these activators interact
has a dominant negative effect on their activity (27, 32, 41,
44). Similar experiments have shown that hTAFII105
interacts specifically with the p65 subunit of NF- There is also evidence that TAFIIs are involved in nuclear
receptor (NR) function. The activity of NR activation function 2 (AF-2)
requires a ligand-induced conformational change in the ligand-binding
domain (LBD) which brings the AF-2 activating domain (AD) core in
In this report, we provide evidence that hTAFII55 is
involved in the activity of some NRs. We show that hTAFII55
selectively interacts with the LBDs of the human VDR and chicken TR Construction of recombinant plasmids.
The
hTAFII55 and NR expression vectors used were previously
described (22, 26, 28, 29, 31). All of the G4-VDR, TR Transfection of Cos cells and immunoprecipitations.
Cos
cells were transfected by the calcium phosphate coprecipitation
technique, and immunoprecipitations were performed as previously
described (22, 29). At 48 h following transfection, the
cells were harvested by three freeze-thaw cycles in buffer A (50 mM
Tris-HCl [pH 7.9], 20% glycerol, 1 mM dithiothreitol, 0.1% Nonidet
P-40) containing 0.5 M KCl. The expression of the transfected proteins
was verified on Western blots by using 10-µl cell extract samples.
For immunoprecipitations, 50 µl of the cell extracts was incubated
for 1 h at 4°C with 1 to 2 µg of the indicated monoclonal
antibodies (MAbs), after which time 50 µl of protein G-Sepharose was
added and incubation was continued for another 2 h. The protein
G-Sepharose was then washed four times for 10 min each time at room
temperature with buffer A containing 1.0 M KCl and once with buffer A
containing 0.1 M KCl. The resin was resuspended in sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) loading buffer
and boiled for 5 min, and one-half of the sample was subjected to
SDS-PAGE. The bound proteins were detected on Western blots with the
indicated antibodies by using an ECL kit (Amersham). Where indicated,
ligands were added [50 nM all-trans-RA,
9-cis-RA, and 3,5,3'-triiodo-L-thyronine, and 100 nM 1,25(OH)2D3] at the same time as the
DNA-calcium phosphate coprecipitate. For chloramphenicol
acetyltransferase (CAT) assays, 3 µg of the 17m5-TATA-CAT reporter
plasmid was cotransfected with 2 µg of a Antibody preparation.
MAbs against hTAFII55
(19TA), the B10 epitope, and the G4 DBD (3GV2) were previously
described (1, 22, 26, 29, 49).
hTAFII55 interacts selectively with the LBDs of VDR and
TR
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Human TAFII55 Interacts with the Vitamin
D3 and Thyroid Hormone Receptors and with Derivatives of
the Retinoid X Receptor That Have Altered Transactivation
Properties
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
). Following expression
in Cos cells, hTAFII55 interacts with the VDR and TR
LBDs in a ligand-independent manner whereas no interactions with the
retinoid X receptors (RXRs) or with other receptors were observed.
Deletion mapping indicates that hTAFII55 interacts with a
40-amino-acid region spanning -helices H3 to H5 of the VDR and TR
LBDs but not with the equivalent highly related region of RXR
.
TAFII55 also interacts with chimeric receptors in which the
H3-to-H5 region of RXR has been replaced with that of the VDR or
TR. Furthermore, replacement of two single amino acids of the RXR
LBD with their VDR counterparts allows the RXR LBD to interact with
hTAFII55 while the corresponding double substitution allows
a much stronger interaction. In transfection experiments, the single
mutated RXR LBDs activate transcription to fivefold higher levels
than wild-type RXR while the double mutation activates transcription
to a level comparable to that observed with the VDR. There is therefore
a correlation between the ability of the modified RXRs to interact with
hTAFII55 and transactivation. These results strongly
suggest that the TAFII55 interactions with the modified RXR
LBDs modulate transcriptional activation.
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
B and that
TAFII105 expression strongly potentiates activation by
NF-B in mammalian cells (53). Coexpression of hTAFII28 and/or TBP also strongly potentiates activation by
the viral Tax protein, and Tax interacts directly with
hTAFII28 and TBP to form a ternary complex (11).
-helix H12 into the proximity of -helix H4 of the LBD (8,
40, 48), forming a novel interaction surface and allowing the NRs
to interact with putative transcriptional intermediary factors (TIFs)
(4, 12, 33, 36, 39, 45, 54). Although interaction with TIFs
is required for NR AF-2 function, additional direct or indirect
interactions with the basal transcription apparatus may also contribute
to activity. In support of this, we have shown that expression of
hTAFII135 specifically potentiates activation by AF-2 of
the all-trans-retinoic acid (RA) receptor (RAR), the thyroid
hormone receptor (TR), and the vitamin D3 receptor (VDR) (28) while expression of hTAFII28 potentiates
activation by many NRs, the most dramatic effects being seen with the
receptors for the 9-cis-RA receptor (RXR), the estrogen
receptor (ER), and the VDR (26).
following coexpression in Cos cells. Analysis with VDR deletion mutants shows that hTAFII55 interacts with a 40-amino-acid region
spanning -helices H3 to H5 and containing the NR signature.
hTAFII55 interacts with the isolated H3-to-H5 region of the
VDR and TR but not with the analogous highly related region of
RXR, thus mimicking the selective interactions observed with the
corresponding LBDs. Replacement of one or two amino acids of the RXR
H3-to-H5 region with their counterparts from the VDR resulted in
interactions with hTAFII55. In transfected cells, the
mutant RXR LBDs which interact weakly with TAFII55
activate transcription to fivefold higher levels than wild-type RXR
while the double mutant which interacts strongly with
TAFII55 activates transcription as strongly as the VDR.
These results provide evidence that interaction with
TAFII55 modulates the transactivation properties of the
modified RXR LBDs.
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
, and RXR chimeras were constructed by PCR using the appropriately designed oligonucleotides with restriction sites and cloned into the
vector pXJ440, encoding the DNA-binding domain (DBD) of the yeast
activator GAL4 (amino acids 1 to 147; G4) (52). All plasmids were verified by automated DNA sequencing. Further details of constructions are available on request.
-galactosidase reporter
as an internal control, along with the indicated concentrations of the
G4-RXR expression vectors. After correction for transfection
efficiency using 
-galactosidase assays, CAT assays were performed by
standard protocols and the percentage of acetylated chloramphenicol was
determined by quantitative PhosporImager analysis on a Fujix BAS 2000 apparatus. In all cases, similar results (±20%) were obtained in at
least three independent transfections and the results of typical
experiments are shown.
RESULTS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
.
To look for interactions between hTAFII55 and
transcriptional activators, vectors expressing chimeras comprising the
NR LBDs or the full-length VDR fused to the DBD of the yeast activator G4 were cotransfected into Cos cells along with vectors expressing B10-tagged hTAFII55 (Fig. 1).
Transfected-cell extracts were then prepared, and protein expression
was verified on immunoblots by using MAbs directed against the ER B10
tag (1), hTAFII55 (19TA; 22),
or the G4 DBD (3GV2; 49). Transfected-cell extracts
were then immunoprecipitated with these MAbs, and the precipitated proteins were detected on immunoblots. Analysis of interactions with
hTAFII55 is complicated by the fact that it comigrates with heavy chains of the MAbs used in the immunoprecipitations. For clarity,
some of the Western blots which are presented were revealed only with
MAbs against hTAFII55 or the coprecipitated G4-NR chimera and secondary antibodies against either the light or heavy chains, as
indicated in the figure legends.
View larger version (30K):
[in a new window]
FIG. 1.
Structures of hTAFIIs and nuclear expression
vectors. The pAT6 vectors contain the epitope for MAb B10 at the N
terminus. The amino acid coordinates of the N- and C-terminal
boundaries in each construct are shown. All of the NR expression
vectors are cloned in the pXJ440 vector, where the NR sequences are
fused to the G4 DBD. h, human; m, mouse; c, chicken.
(DE) was precipitated only with the anti-G4 antibody (Fig. 2A,
lanes 1 to 6). However, when coexpressed, both B10-hTAFII55
and G4-TR(DE) were coprecipitated by each antibody,
irrespective of the presence or absence of the ligand [Fig. 2A, lanes
7 to 12; while B10-hTAFII55 and the G4-TR(DE) chimera
have similar electrophoretic mobilities and are difficult to
distinguish in lanes 8 and 11, both proteins can be clearly seen in
lanes 9 and 12, compared with lanes 4 and 6]. Similarly, when
coexpressed with B10-hTAFII55, G4-VDR could be
immunoprecipitated by MAb B10 both in the presence and in the absence
of the ligand (Fig. 2B, lanes 1 to 4). In contrast, no coprecipitation
of hTAFII55 with the G4 chimeras of the RXR
[G4-RXR(DE); Fig. 2C, lanes 4 to 9] or RAR (data not shown) LBDs
was observed. Thus, under the same stringent conditions used to detect
TAF-TAF interactions (i.e., washing with a buffer containing 1.0 M
KCl), hTAFII55 formed a stable, salt-resistant,
immunoprecipitable complex selectively with the VDR and TR LBDs in a
ligand-independent manner.
|
-helices H1 and H2 of the E domain, whereas G4-VDR
E(196-427), containing the remainder of the E domain, was
coimmunoprecipitated with B10-hTAFII55 (data not shown). To
further delineate the amino acids of the E region required for
interaction with hTAFII55, a further series of G4-VDR E
chimeras (see Fig. 4A) were expressed either alone or together with
B10-hTAFII55 (for example, Fig. 3A). As several of these chimeric fusion
proteins comigrated on SDS-PAGE with the light chains of the MAbs used
in the immunoprecipitations, the transfected-cell extracts were
precipitated with the anti-G4 MAb and the presence of the
coprecipitated B10-hTAFII55 was revealed by using MAb B10
or vice versa.
|
|
-helices H8 and H9, allow interaction with
hTAFII55 (summarized in Fig. 4A). This second
hTAFII55-interacting region was more precisely mapped.
G4-VDR E(324-341), containing -helix H8, was coprecipitated with
B10-hTAFII55 (Fig. 3C, lanes 7 and 8), while no
coprecipitation of G4-VDR E(342-373) or G4-VDR E(374-411), containing
-helices H9 and H10 and -11, respectively, was observed (lanes 9 to
12). In agreement with this result, interaction between VDR(DE) and
hTAFII55 was not affected by deletion of the AF-2 AD core
located in -helix H12 between amino acids 411 and 427 (data not
shown; Fig. 4A). Therefore, interaction between the C-terminal moiety
of the VDR E region and hTAFII55 requires -helix H8 but
not -helices H9 to H11 nor the AF-2 AD core, which is required for
ligand-dependent interactions of NRs with various TIFs (summarized in
Fig. 4A).
The above-described results indicate that hTAFII55
selectively interacts with two independent regions of the VDR E domain: a region spanning -helices H3 to H5 containing the NR signature and
-helix H8.
Selective interaction of hTAFII55 with the H3-to-H5 NR
signature-containing regions of the VDR and TR.
The
above-described results show that hTAFII55 interacts with
the VDR H3-to-H5 region containing the NR signature. This region contains many well-conserved amino acids (boxed in Fig. 4B) involved in
intramolecular interactions required to stabilize the canonical NR fold
(51). The high conservation in this region of the NR LBDs
(51; Fig. 4B) led us to compare the binding of
hTAFII55 to the equivalent regions of chicken TR and
RXR. G4 chimeras containing these H3-to-H5 regions [G4-TR
E(220-260) and G4-RXR E(273-313)] were coexpressed along with
B10-hTAFII55. G4-TR E(220-260) was specifically
precipitated along with B10-TAFII55 (Fig. 3D, lanes 7 to
10). In contrast, no coprecipitation of G4-RXR E(273-313) was
observed (Fig. 3D, lanes 3 to 6). The selective binding of hTAFII55 to the H3 to H5 region of the VDR and TR, but
not the RXR, LBDs therefore mimics the specificity seen when the
complete LBDs of these NRs were used.
H3-to-H5 regions can
promote interactions with hTAFII55, we created chimeric
RXR(DE)s where amino acids 273 to 313 of RXR containing the
H3-to-H5 region have been replaced with the equivalent amino acids of
the VDR or TR E domain (G4-RXR-VDR-RXR and G4-RXR-TR-RXR; Fig.
5A). These chimeras were coexpressed
along with hTAFII55. As described above for G4-RXR, no
coprecipitation of hTAFII55 with G4-RXR(DE) was observed
(Fig. 5B, lanes 3 and 4). In contrast, the RXR-VDR-RXR and RXR-TR-RXR
chimeras were coprecipitated with hTAFII55 (Fig. 5B, lanes
1, 2, 5, and 6). Thus, the VDR or TR H3-to-H5 regions can mediate
interactions with hTAFII55 when transferred to the G4-DBD
either alone or in the context of the RXR DE region. In the converse
experiments, deletion of the VDR and TR H3-to-H5 regions or their
replacement with that of the RXR did not abrogate TAFII
interaction with these LBDs, in agreement with the observation that
-helix H8 can also interact with hTAFII55 (data not
shown).
|
Single amino acid changes in the RXR LBD induce interactions
with hTAFII55.
The selective interaction of
hTAFII55 with the H3-to-H5 regions of the VDR and TR but
not RXR is surprising considering the high degree of sequence
homology between these receptors in this region (Fig. 4B). We
therefore reasoned that exchanging solvent-exposed amino
acids of RXR with those of the VDR might recreate the
TAFII55 interaction surface. Two positions on the exposed
surface were chosen where the RXR amino acids are radically different
from those in the VDR, i.e., F278 in H3 and L295 in H4 (Fig.
6A). At these positions, there are polar
amino acids in the VDR while there are bulky hydrophobic residues
in the RXR.
|
(DE) (m1,
F278Q; m2, L295S; m3, F278Q/L295S; Fig. 6A) and coexpressed with
hTAFII55, and interactions were verified by
immunoprecipitation with the anti-G4 antibody. No significant
coimmunoprecipitation of B10-hTAFII55 was observed when it
was expressed alone or with wild-type (WT) G4-RXR(DE) (Fig. 6B, lanes
2, 5, and 7). B10-hTAFII55 was coprecipitated with both
G4-RXR(DE) m1 and m2 (lanes 3, 4, 8, and 10); however, this interaction
was weaker than that observed with the VDR (lanes 1 and 6). In
contrast, a strong interaction, comparable to that seen with the
VDR, was observed with the double mutant m3 (compare lanes 6 and 9).
Therefore, exchange of amino acids between the RXR and VDR
LBDs can recreate a surface, allowing interactions with
TAFII55. Single amino acid changes allow a weak interaction, while the double substitution allows a much stronger interaction.
Transactivation is modulated by mutations in the RXR
H3-to-H5 region which allow interaction with hTAFII55.
To test whether these novel interactions could affect the
transcriptional activation properties of the mutated RXR LBDs,
increasing quantities of vectors expressing the WT or mutated
G4-RXR(DE) chimeras were cotransfected along with a G4-responsive
CAT reporter (see Materials and Methods and references
26 and 28). As previously described (26), the WT RXR LBD activated transcription
only weakly from this promoter (Fig. 7,
lanes 4 and 5) while strong activation by the VDR LBD was seen (lanes 2 and 3). In contrast to the WT RXR, mutants m1 and m2 activated
transcription up to five times more than the WT (lanes 6 to 9) whereas
mutant m3 activated transcription to a level comparable to that seen
with the VDR (lanes 2 and 3 and lanes 10 and 11). Immunoblot
experiments showed equivalent expression levels of each of these
activators (data not shown). These results reveal a correlation between
the interaction of the mutated RXR LBDs with TAFII55 and
their ability to activate transcription (summarized in Fig. 6A),
providing evidence that this interaction is involved in transcriptional
activation.
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DISCUSSION |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
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Novel interaction surfaces in the VDR LBD.
We describe here
novel interactions between the LBDs of the VDR and TR with a
component of transcription factor TFIID. Following coexpression in Cos
cells, hTAFII55 could be specifically coprecipitated with
the LBDs of the VDR and TR, irrespective of the presence of the
ligand. The selectivity of the interactions is shown by the observation
that under the same conditions, no interactions between
hTAFII55 and other NRs were observed.
-helices H3 to H5 and containing the NR
signature. Fusion of this region to the G4 DBD is sufficient to mediate
interactions with hTAFII55, showing that although the NR
LBD is highly structured, this domain can interact with
hTAFII55 even when presented in a different context. This
is therefore an autonomous domain which can mediate interactions with
hTAFII55. hTAFII55 interacted with the H3-to-H5
regions of the VDR and TR, but not RXR, hence mimicking the
selectivity seen with the corresponding full-length NR LBDs. Moreover,
replacement of the RXR H3-to-H5 region with that of TR or the VDR
is sufficient to induce TAFII55 interactions with the
RXR LBD.
When exposed amino acids Q278 and L295 in H3 or H4 of the RXR LBD
are replaced with their VDR counterparts, novel interactions with
TAFII55 are observed. Thus, despite the high degree of
conservation of the H3-to-H5 region among the NRs, due to the presence
of the signature, these regions of the VDR and TR also contain amino acids which dictate selective NR-hTAFII interactions.
Comparison of the amino acids required for hTAFII55
interactions with those required for interaction with the LXXLL motif in several TIFs (19, 23) shows that these two sites are
close to each other but not identical. VDR amino acids Q239 and S256 and their RXR equivalents are located on the surface surrounding the
hydrophobic cleft created by the juxtaposition of hydrophobic amino
acids of the NR signature with amino acids of H12, which is required
for TIF interactions (16, 33). Interaction with TAFII55 does not require this hydrophobic cleft, as there
is no requirement for the H12 helix. Moreover, mutation of the amino acids in the human TR LBD equivalent to Q239 and S256 (T281 and C298) had no effect on interaction with the LXXLL motif of GRIP1. The
amino acids which are critical for TAFII55 interaction are not part of the canonical NR signature and are not essential for interaction with TIFs bearing LXXLL motifs. There are therefore two
surfaces in this region of the VDR and TR LBDs specifying interactions
with distinct cofactors.
Although mutation of amino acids F278 and L295 in RXR to their VDR
counterparts suffices to allow interaction with TAFII55, the converse mutations in the VDR LBD do not abolish interaction with
TAFII55 or transactivation (our unpublished data). It is probable that the RXR mutations define a minimal surface
required for interaction with hTAFII55 but that in the VDR
other amino acids also contribute to the interactions. In
addition, it should be remembered that TAFII55 also
interacts with amino acids in H8 and that this interaction is not
affected by the mutations in the H3-to-H5 region.
The second VDR region interacting with hTAFIIs is located
between amino acids 324 and 341, corresponding to -helix H8. A molecular model of the VDR LBD generated from sequence alignments and
comparison with the known structures of the RXR, RAR, and TR LBDs
suggests that only amino acids at the N- and C-terminal extremities of
H8 would be solvent exposed, the remainder being buried in the
structured LBD. The C-terminal end of H8 and the L8-9 loop presents
most of the exposed residues and is therefore the most likely
hTAFII interaction site.
Mutant RXR LBDs which interact with TAFIIs have
altered transactivation properties.
The results presented here
provide strong evidence that the interaction between
TAFII55 and the mutated RXR LBDs may promote transcriptional activation in mammalian cells. Two single amino acid substitutions in the RXR LBD which allow interaction
with TAFII55 also enhance transcriptional activation.
The double mutation which induces a much stronger interaction with the
RXR LBD, comparable to that seen with the VDR, activates transcription
to levels comparable to that seen with the VDR. In the case of the RXR,
there is therefore a correlation between interaction with
hTAFII55 and transactivation potential. The presence of
multiple TAFII55 interaction sites in the VDR LBD
complicates the reciprocal loss-of-function analysis which would
require the simultaneous mutation of both regions. However, by analogy
with what is observed with the RXR, it is possible that the VDR- or
TR-TAFII55 interaction also contributes to the
transcriptional activity of these activators.
LBD is somewhat analogous
to that described in yeast with the GAL11 and GAL11P proteins, where a
novel interaction with the G4 DBD induced by a fortuitous
mutation in the holoenzyme component GAL11 (GAL11P) suffices to
activate transcription (3, 38). Here, we show that mutations
which induce RXR-TAFII55 interactions are also sufficient to convert the RXR LBD from a weak activator to a much
stronger activator, providing evidence that the novel interactions with
hTAFII55 potentiate transcriptional activation in mammalian cells.
Our results favor the two-step model which has been proposed for NR
function. Upon ligand binding, the NR LBDs interact with the TIFs with
histone acetyltransferase activities and induce chromatin remodelling
(45 and references therein). Following this step,
our results and those of others suggest that transactivation by NRs may
involve additional interactions with TAFIIs and/or other
components of the general transcription machinery, for example, TFIIB
for the VDR and the TR (2, 7, 24), hTAFII30 for the ER (21), and TBP and/or drosophila TAFII110
for the RXR and the TR (37, 42). In this respect, it is
important to note that, unlike hTAFII55, most TIFs interact
with each of the NR LBDs with comparable affinities yet the RXR LBD is
a considerably weaker activator than the VDR or TR LBD, at least with
our test promoter. Therefore, although interaction with TIFs and
chromatin remodelling are essential steps, additional interactions such as those described here with hTAFII55 may well contribute
to activation by a given LBD.
A similar model has been proposed for the cyclic AMP response
element-binding protein (CREB), where phosphorylation-induced interaction with the CREB-binding protein, also one of the NR TIFs, and
a constitutive interaction with TAFII135 have been shown to
be required for transactivation (32). A requirement for
inducible interactions with cofactors allows activators which respond
to extracellular stimuli (hormones or mitogens) to integrate these signals with basal transcription machinery interactions required for activation.
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ACKNOWLEDGMENTS |
|---|
We thank P. Chambon for support; L. Carré for excellent technical assistance; L. Perletti for critical comments; S. Vicaire and D. Stephane for DNA sequencing; Y. Lutz and the MAb facility, the staff of the cell culture and oligonucleotide facilities, B. Boulay, J. M. Lafontaine, R. Buchert, and C. Werlé for illustrations; and Roussel-Uclaf for providing 1,25(OH)2D3.
G.M. and A.-C.L. were supported by fellowships from the Ligue Nationale contre le Cancer and the Association pour la Recherche contre le Cancer. This work was supported by grants from the CNRS, the INSERM, the Hôpital Universitaire de Strasbourg, the Ministère de la Recherche et de la Technologie, the Association pour la Recherche contre le Cancer, the Ligue Nationale contre le Cancer, and the Human Frontier Science Programme.
A.-C.L. and G.M. contributed equally to this work.
| |
FOOTNOTES |
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* Corresponding author. Mailing address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163-67404, Illkirch Cédex, C.U. de Strasbourg, France. Phone: 33 3 88 65 34 40 (45). Fax: 33 3 88 65 32 01. E-mail: irwin{at}titus.u-strasbg.fr.
Present address: EMBL, 69012, Heidelberg, Germany.
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REFERENCES |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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) of
each region with hTAFII55 is summarized on the right. The
amino acid sequence of the VDR H3-to-H5 region is shown at the bottom.
Conserved amino acids which form the signature are indicated above the
sequence. The filled squares below the amino acids indicate amino acids
which may be exposed on the surface of the VDR LBD. (B) Alignment of
the signature regions of the VDR, chicken (c) TR
