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-Chain Gene
,
*
Bioscience Research and Development Laboratory, Asahi Breweries, Ibaraki, Japan; and
Department of Immunology and
Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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RI 
-chain, a component of the high-affinity IgE
receptor primarily responsible for IgE-dependent allergic response,
were investigated. Two regions, -74/-69 and -55/-47, which
contained binding motifs for proteins belonging to the Ets family and
the GATA family, respectively, were shown to be necessary for the
activation of the -chain promoter. Both the regulatory elements
enhanced the promoter activity only in -chain-producing cells PT18
and RBL-2H3 (mast cell lines), indicating that the elements required
specific trans-acting proteins present in the
-chain-producing cells. EMSA using nuclear extracts and in
vitro-translated proteins revealed that Elf-1 and GATA-1 bound to the
enhancer elements. This is the first report describing the regulation
in the expression of the FcRI -chain. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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RI)2 triggers
the release of a variety of chemical mediators from activated mast
cells, which results in allergic responses.
FcRI is a tetrameric receptor composed of one -, one ß-, and
two 
-chains. The -chain is composed of two critical regions, a
single membrane-spanning domain and a cytoplasmic domain that contains
the immunoreceptor tyrosine-based activation motif (1)
sequence for the association of Syk tyrosine kinase. The -chain is
also served as a common component of other Ig Fc receptors, such as
low-affinity receptor for IgG (FcRIII), high-affinity receptor for
IgG (FcRI), and Fc receptor for IgA (FcR), and is also associated
with the TCR-CD3 complexes (2, 3, 4, 5, 6, 7). Thus, in contrast with
the expression of FcRI in the limited cells, the subunit is
found in various kinds of cells, suggesting that the subunit is not
directly involved in the regulation of FcRI expression. The
ß-chain, which also has immunoreceptor tyrosine-based activation
motif to associate with Lyn (8), is known to amplify the
-chain-mediated cell-activation signals (9, 10).
However, the ß-chain is shown to be unnecessary for the expression of
functional human FcRI on the cell surface (11). On the
other hand, the -chain is a specific component of FcRI and is
known to bind to the Fc region of IgE Ab (12, 13).
Recently, the expression of FcRI on human mast cells
(14, 15, 16) or on eosinophils (17) was found to
be up-regulated by IL-4. Messenger RNA for the -chain was
specifically increased by IL-4, while the transcription levels of the
ß-chain and the -chain were not changed through the stimulation.
All of these observations suggest a crucial role of the -chain in
the regulation of the FcRI expression. Necessity of the -chain
for FcRI-mediated allergic reaction was also observed in
-chain-deficient mice as well as human (18). In
addition, when human -chain gene was introduced in mouse cells, the
human FcRI -chain transgenic mice have a cell expression pattern
of human -chain that is indistinguishable from that seen in humans
(10, 19). This indicated the presence of a common
mechanism for -chain expression in mammalian cells. To reveal
mechanisms of the FcRI expression, which might contribute to
manipulation of the IgE-mediated allergic response, we analyzed
regulatory elements for human FcRI -chain gene and determined
trans-acting proteins binding to the elements, which enhance
the transcription of the -chain specifically in mast cells.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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PT18 (mouse mast cell line) and Jurkat (human T cell line) cells
were cultured in RPMI 1640 medium (Nissui Pharmaceutical, Tokyo, Japan)
containing 10% FBS (Life Technologies, Rockville, MD), glutamine (300
mg/L), penicillin (100 U/ml), and streptomycin (100 µg/ml), and
RBL-2H3 (rat mast cell line) cells were grown in minimum essential
medium (-MEM) (Life Technologies) supplemented with 10% FBS and
penicillin/streptomycin at 37°C in 5% CO2
incubator.
Plasmid construction
The human genomic DNA of the FcRI -chain was isolated from
a human genomic library (Stratagene, La Jolla, CA) by plaque
hybridization using human FcRI -chain cDNA as the probe. The
5'-flanking region of about 1.3 kb including an untranslated region of
the first exon of the -chain gene was prepared by PCR using
5'-GCaagcttGATCTTCATGTGGAATGACTGG-3' and
5'-CAGGAGccATGGTCTTCATGGA-3' (replaced
nucleotides were shown as small letters to introduce the
HindIII and NcoI site, which were shown as
italic, and the initiation codon was represented as bold) as the
primers and the human FcRI -chain gene as the template, and
subcloned into the HindIII-NcoI site of pGV-B2
(Promega, Madison, WI). The resulting plasmid was named pGV-B-HN1.3
(Fig. 1
; nt -1256 to nt +29). The
plasmid pGV-B-KN2.4 containing a further upstream region, as shown
at the bottom bar in Fig. 1, was constructed as follows. An 
1.8-kb
(nt -2437 to nt -602) fragment of the 5'-franking region was obtained
from the human FcRI -chain gene using original the
KpnI/NheI site, and was ligated to pGV-B-HN1.3
digested with KpnI/NheI. Other plasmids
containing a variety of 5'-truncation of the -chain promoter region
connected to the upstream region of the luciferase structural gene were
constructed in a similar way using several restriction endonucleases
and exonuclease III (Takara Shuzo, Kyoto, Japan) and/or by
PCR.
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Transfection and luciferase assay
The cells were grown to 90% confluence (RBL-2H3), and 1
x 106 cells/ml (PT18 and Jurkat) were washed
with ice-cold medium including 10% FBS and resuspended in the same
medium. The cells (5 x 106 cells in 0.5 ml)
were cotransfected with 5 µg of the test construct and 25 ng of
pRL-CMV (Promega) by electroporation using a Bio-Rad Gene Pulsar II
(Hercules, CA) set at 300 V and 950 µF. The pRL-CMV plasmid carrying
Renilla luciferase gene was cotransfected and used for
normalizing the transfection efficiency. The pGV-P2 (Toyo ink; Tokyo,
Japan) was used as an internal control to compare each different
experiment. The measurement of luciferase activity was conducted using
a Dual-luciferase assay kit (Promega) essentially according to
manufacturer’s instructions. Briefly, cells were harvested 20–24 h
after transfection, washed twice with PBS, pH 7.4, and then lysed with
100 µl of lysis buffer (included in the Dual-luciferase assay kit)
for 15 min. Ten microliters of the lysate was mixed with 100 µl of
Luciferase Assay Reagent II, and the luminescence was immediately
measured by a luminometer (Model LB9501; Berthold, Postfach, Germany).
After the measurement of luciferase activity, 100 µl of Stop & Glo
Reagent included in the Dual-luciferase assay kit was added to the
reaction mixture, and the Renilla luciferase activity was
determined as an internal control to normalize the transfection
efficiency.
Nuclear extract preparation
PT18 cells (2 x 107 cells) were washed with ice-cold PBS and resuspended in 1.2 ml of buffer A (10 mM HEPES, pH 7.9, 10 mM KCl, 0.1 mM EDTA, 1 mM DTT, 1 mM PMSF, 1 µg/ml leupeptin, and 1 µg/ml aprotinin) for 10 min at 4°C. The cells were incubated for an additional 15 min with 0.5% Nonidet P-40 for cell lysis. The lysates were centrifuged at 6000 x g for 1 min, and the pellets were resuspended in 100 µl of extract buffer (20 mM HEPES, pH 7.9, 400 mM KCl, 1.5 mM MgCl2, 0.2 mM EDTA, 1 mM DTT, 1 mM PMSF, 1 µg/ml leupeptin, and 1 µg/ml aprotinin). After incubation for 1 h on ice, the lysates were centrifuged at 6000 x g for 5 min and the supernatant was collected. Glycerol was added to 15%, and the extract was stored at -70°C until use. Protein concentrations were determined by a commercially available kit (Bio-Rad).
The nuclear extract from RBL-2H3 was prepared by the method slightly different from that described above. RBL-2H3 cells (5 x 107) washed with ice-cold PBS were resuspended with 1.0 ml buffer A and were immediately centrifuged at 1000 x g for 5 min. The pellets were resuspended with 1.0 ml buffer A including 0.05% Nonidet P-40 and incubated for 1 min on ice. The lysates were centrifuged at 3000 x g for 1 min and the pellets were resuspended with 315 µl of modified extract buffer (10 mM HEPES, pH 7.9, 50 mM KCl, 0.1 mM EDTA, 1 mM DTT, 1 mM PMSF, 1 µg/ml leupeptin, 1 µg/ml aprotinin, and 10% glycerol). After addition of 35 µl of 3 M (NH4)2SO4 to the nuclear extract, the suspension was incubated for 30 min on ice. After centrifugation at 6000 x g for 15 min, equal volumes of 3 M (NH4)2SO4 were added to the supernatants to precipitate the nuclear proteins. The pellets obtained by centrifugation at 10,000 x g for 15 min were resuspended with appropriate volume of modified extract buffer.
Electrophoretic mobility shift assay
The double-stranded oligonucleotide probes for EMSA were prepared as follows. The probes 5'-GATACAGAAAACATTTCCTTCTGCTTTTTGGTTTTA-3' and 5'-GGCTTAAAACCAAAAAGCAGAAGGAAATGTTTTCTG-3' were annealed by incubation at 95°C for 5 min and successive gradual cooling to 37°C. The double-stranded DNA was 5'-end-labeled with [32P]ATP and T4 polynucleotide kinase (Promega). After Klenow fragment (Promega) treatment, labeled oligonucleotides were purified using a ProbeQuant G-50 micro column (Pharmacia Biotech, Uppsala, Sweden). The labeled double-stranded DNA containing the sequence motif for Ets (nt -68 to nt -29) was named probe 1. Another labeled double-stranded DNA named probe 2 containing the sequence motif for GATA (nt -77 to nt -58) was prepared by two oligo nucleotides, 5'-ACCAGATATGATACAG-3' and 5'-TTTTCTGTATCATATC-3', in a similar way. The reaction mixtures (15 µl), containing 4 µg of nuclear extract, 350 ng of poly(dI-dC), 1 mM MgCl2, 30 mM KCl, 10 mM HEPES, pH 7.9, 1 mM DTT, and 5% glycerol were preincubated at room temperature in the absence of the probe for 15 min and incubated for an additional 15 min at room temperature with the radiolabeled probe (5 x 104 cpm). The reaction mixtures were then subjected to electrophoresis with a native 4% polyacrylamide gel at 120 V for 2.5 h in 0.5x TBE buffer (45 mM Tris-borate, pH 8.0, 45 mM boric acid, 1 mM EDTA). For competition experiments, unlabeled blunt-ended competitor oligonucleotides were added to the binding reaction mixtures before the addition of the radiolabeled oligonucleotide probe. For the supershift or inhibition experiments by Abs, 1.0 µg of Abs was added to the reaction mixtures and incubated for 15 min. The labeled probe was then added to the reaction mixture and the mixture was incubated for an additional 15 min, then applied onto a native 4% polyacrylamide gel for electrophoresis. The anti-Elf-1, anti-Ets-1/2, anti-GATA-1, anti-GATA-2, and anti-GATA-3 Abs were purchased from Santa Cruz Biotechnology(Santa Cruz, CA). All gels were dried and subjected to autoradiography. Modifications are described in the figure legends.
In vitro transcription and translation of GATA-1 and Elf-1
Both of the rat GATA-1 cDNA and rat Elf-1 cDNA were obtained with mRNA from RBL-2H3 cells by using Trizol reagent (Life Technologies) and a RT-PCR kit (Takara Shuzo). Two synthetic oligonucleotides, 5'-GTTAAACCCCAGTGTCCACATGGATTTTCCTGGTCTA-3' and 5'-CCTTCAAGAACTGAGTGGAGACACTACGCTAG-3', were used as primers to amplify rat GATA-1 cDNA according to reported nucleotide sequence (20). As primers for amplification of rat Elf-1 cDNA, we used the following oligonucleotides derived from mouse Elf-1 cDNA (21); 5'-ATGGCTGCTGTTGTCCAACAGAACGACCTA-3' and 5'-TTAAAAAGAGTTGGGCTCTAGCAGTTCATT-3', because the nucleotide sequence of rat Elf-1 cDNA has not been published until now. Rat Elf-1 cDNA was obtained using a rat intestine cDNA library (Clontech Laboratories, Palo Alto, CA) using the amplified PCR products as the probe, and its nucleotide sequence was determined (C. Nishiyama et al., manuscript in preparation). These cDNA fragments, both of rat GATA-1 and rat Elf-1, were inserted to the expression plasmid pCR3.1 (Invitrogen, Leek, The Netherlands), and the resulting plasmids were used for in vitro transcription and translation using TNT; T7 Quick-coupled transcription/translation system (Promega).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-chain promoter region is activated only in
-chain-producing cells
Previous studies by Fung-Leung et al. with transgenic mice
suggested that 1.3 kb upstream of the human FcRI -chain-coding
region contained all the elements sufficient for cell type-specific
expression of the FcRI -chain in mouse cells (19).
For elucidation of the transcriptional control enhancer of human
-chain gene, we used two rodent cell lines, RBL-2H3 and PT18, which
were known to express FcRI constitutively. In this study, a DNA
fragment containing 2.4 kb upstream of the translational initiation
codon for the -chain was cloned into the
KpnI-NcoI site of pGV-B2 carrying the luciferase
gene from Photinus pyralis as reporter. For identification
of cis-activating elements of the promoter, several deletion
constructs carrying the upstream sequences in various length ranging
from 2.4 kb to 100 bp upstream of the translational start site were
generated and introduced into FcRI-positive cells, RBL-2H3 and PT18,
and negative cells, Jurkat. As shown in Fig. 1
, no constructs including
the translational start site showed detectable luciferase activity in
Jurkat. This indicated that Jurkat cells did not contain components
promoting the transcription of FcRI -chain gene. Even the
shortest region containing 100 bp upstream of the translational start
site demonstrated promoter activity higher than that of SV40 promoter
in RBL-2H3, suggesting the region contained the promoter of FcRI
-chain gene that gave the transcription at a sufficient level.
In PT18, each construct gave the luciferase activity at almost the same
level, which was contrast with the case of RBL-2H3, where longer DNA
fragment gave higher luciferase activity. This may suggest that the
amount of transcription factors recognizing the promoter region and/or
proteins affecting the transcription efficiency was different. In any
cases, these results indicated that the -chain promoter was
functional only in the FcRI-positive cells, although regulation was
somewhat different between RBL-2H3 and PT18 cells.
The enhancer element up-regulates the activity of heterologous promoters
The above-mentioned results suggested that the cloned upstream
region of the -chain gene included its own promoter and possible
enhancer elements responsible for initiating the transcription of the
-chain gene in -chain-producing cell lines. For determining the
location of the elements, we used several constructs in which a portion
of the promoter region of the -chain gene was replaced by a
heterologous promoter, SV40, or thymidine kinase promoter. All the
constructs lacked the transcription initiation site of -chain to
decrease the transcription from -chain promoter.
As displayed in Fig. 2A, when
the luciferase gene was connected upstream of SV40 or thymidine kinase
promoter, the luciferase activity raised up to above four or five times
compared with the basal activity by the construct containing only
either of SV40 or thymidine kinase promoter in RBL-2H3. In addition,
this effect was not observed in Jurkat as expected. This suggested that
the fragment from nt -605 to nt -8 contained the element that
increased the promoter activity in the specific cells. Consistent with
this, when the fragment from nt -1256 to nt -8 was placed in the
opposite orientation to the SV40 promoter, increased luciferase
activity was again observed (Fig. 2B). This indicated that
the fragment contained cis elements up-regulating the
promoter present in its neighborhood. As will be described below, two
transcription factors actually bound the upstream region. Hereafter we
therefore called the elements as the enhancers for -chain gene. We
next performed precise mapping of the putative enhancer elements
through generating various deletion constructs. The -chain gene
fragment from nt -605 to nt -8 had transcription-enhancing activity
equivalent to that demonstrated with the fragment from nt -1256 to nt
-8 even on the heterologous promoter as well as its own promoter. This
suggested that the region nt -605 to nt -8 contained major elements
up-regulating the transcription of the -chain gene. Further deletion
from nt -605 to nt -368 had no effect on the promoter activity.
However, the deletion from nt -85 to nt -8 drastically decreased the
activity, suggesting that the region from nt -85 to nt -8 contained a
enhancer element. Principally the same results were also obtained with
PT18 as the host (data not shown).
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The aforementioned results indicated the presence of enhancer
element in the region between nt -85 and nt -8. Therefore, we
performed fine mapping of the enhancer element by introducing the
mutations into the region from nt -91 to nt -8 of the -605/-8
fragment. For this purpose, nine mutant genes in which three to six
nucleotides were replaced by others were generated by site-directed
mutagenesis. The analysis revealed that the mutations around nt -75
and nt -50 drastically decreased the enhancing activity in both
RBL-2H3 and PT18 cells (Fig. 3). This
suggested the presence of two enhancer segments in this region.
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We next analyzed, by EMSA, the nuclear factors from the
-chain-producing cells that specifically bound to the upstream
region around nt -50. As shown in Fig. 4, nuclear extract prepared from PT18
contained protein(s) that could bind to this fragment (-68/-29).
Electrophoretic mobility shift, showed by an arrow in Fig. 4, was
inhibited when excess amounts of the same but unlabeled fragment was
used as a self-competitor (Fig. 4, lanes 3,
4, and 5). Furthermore, the competitive effect
was not observed when the double-stranded DNA with the following
sequence, GATACAGAAAACATaTgcgTCTGCTTTTTGGTTTTAAGCC, which contained
the base substitutions -54/-50, decreasing enhancer activity,
was applied as a competitor (see Fig. 3 and Fig. 4, lanes 6, 7, and 8). This result
suggested that the shifted band was the complex of the oligonucleotide
with the nuclear protein responsible for the promoter-enhancing
activity. The region around -54/-50 contained the nucleotide sequence
TTTCCTT, which was similar to that of the Ets motif, TTCC, especially
the Elf-1 motif, T/CTTCC
T/G (22).
Then, we synthesized double-stranded oligonucleotide containing the Ets
motif of human GM-CSF promoter (23) and performed similar
EMSA using the oligonucleotide as the competitor. The competitor
inhibited the binding of the nuclear protein(s) to the probe DNA (Fig. 4, lanes 9, 10, and 11). Therefore,
this observation suggests that the nuclear protein binding to the Ets
motif of GM-CSF promoter also bound to the enhancer element of the
-chain gene in mast cell line PT18.
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-chain gene
is Elf-1
The promoter of GM-CSF contains AP-1 motif just upstream of the
Ets motif, forming conserved lymphokine element 0 (CLE0) motif. Elf-1
or Ets-1 was identified as the transcription factor binding to CLE0 of
GM-CSF promoter and IL-5 promoter in T cells (23, 24, 25, 26, 27). To
identify nuclear protein(s) binding to the -chain enhancer, we
examined the effects of anti-transcription factor Abs on the EMSA
profile. As demonstrated in Fig. 5A, when anti-Elf-1 mAb
was added to the reaction mixture, the shifted band drastically
decreased and faint but obvious super shift was observed. On the other
hand, anti-Ets-1/2, GATA-1, GATA-2, and GATA-3 Abs did not show any
effect on the EMSA profile.
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To confirm that Elf-1 bound to the Ets motif, rat Elf-1 cDNA was
cloned from RBL-2H3 cells and expressed by in vitro
transcription/translation system. The rat Elf-1 produced in vitro
actually bound to the oligonucleotide containing the Ets motif (Fig. 5B), and the DNA-Elf-1 complex showed mobility identical
with that seen with the nuclear protein (data not shown). When
anti-Elf-1 Ab was added, faint but apparent super shift and
disappearance of the shifted band were also observed. These results
indicate that the nuclear protein binding to the Ets motif of FcRI
-chain gene is a transcription factor, Elf-1.
Transcription factor binding to the sequence around -75 is GATA-1
To identify the transcription factor that recognizes the sequence
around -75 of FcRI -chain gene, EMSA was conducted. For this
purpose, a double-stranded DNA, probe 2 (nt -77 to nt -58),
containing the critical region for the enhancer activity was used for
EMSA. Specific binding to probe 2 was observed when nuclear proteins
extracted from PT18 were applied (Fig. 6A), which suggested specific
nuclear factors actually bound to the DNA region. The
promoter-enhancing region around -75 contained a motif of GATA,
suggesting a member of the GATA protein family is responsible for the
enhancing activity of FcRI -chain gene expression (see Fig. 3). A
shifted band showing the probe-protein complex disappeared only by
addition of anti-GATA-1 Ab among the three anti-GATA-1, -2, and
–3 Abs. This indicated that the GATA motif was recognized by GATA-1.
To confirm this possibility, similar EMSA was conducted with in
vitro-translated GATA-1 (see Materials and
Methods). The in vitro-translated GATA-1 caused a
mobility shift similar to that shown by RBL-2H3 and PT18 nuclear
extracts (Fig. 6B). Furthermore, the addition of
anti-GATA-1 Ab again inhibited the binding of the GATA-1 and the
oligonucleotide. Therefore, we concluded that the transcription factor
that bound to the GATA motif in the -chain gene promoter was
GATA-1.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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RI -chain gene to up-regulate its
expression. When the upstream sequence was aligned with the sequences
of corresponding regions of murine and rat -chain genes, the
sequences of the two enhancer elements were found to be highly
conserved (Fig. 7) (28, 29, 30).
This suggests that the expression of the -chain is regulated by the
two transcription factors in rodents or other mammals as well as
human.
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-chain gene, the GATA motif (-74/-69) was recognized by
GATA-1 and the Ets motif (-55/-49) was recognized by Elf-1 (Fig. 7).
GATA-1 is known to be indispensable for erythropoiesis (31, 32) and is expressed in cells of myeloid lineage (erythroid
cells, mast cells, megakaryocytes, eosinophils, and basophils)
(33, 34, 35, 36, 37), with the exception of a testis-specific form
transcribed from an alternative promoter (38). Elf-1 was
initially found in T cells as the transcription factor that was
required for the TCR-mediated trans-activation of HIV-2 gene
expression (39). Recently, another role of Elf-1 as a
trans-activation factor for cell-specific gene expression
was found in megakaryocytes, B cells, and macrophages. In addition,
there is evidence showing involvement of Elf-1 in the regulation of a
number of lymphocyte-specific genes, IL-2 (40), IL-2
receptor -chain (41), GM-CSF (23), CD4
(42), IL-3 (43), and IgH (44)
genes. This study revealed an additional role of Elf-1 in the
expression of FcRI -chain. Though either Elf-1 or GATA-1 is
expressed in several cells, all the cells expressing FcRI -chain
contain both of Elf-1 and GATA-1. This indicates both factors are
essential for the expression of FcRI -chain gene. Because both
the GATA-1 and Elf-1 transcription factors are thus obligatory required
for the expression of FcRI -chain (Table I), other FcRI -chain-producing
cells, such as Langerhans cells, could express these transcription
factors.
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RI, production and release of
the Th2-type cytokines were also induced in mast cells
(49, 50, 51). In T cells, several transcription factors,
Elf-1, NF-AT, and HMG-1, were present and promote the expression of the
genes under the control. Interestingly, although the IL-5 promoter has
a GATA motif just upstream of a CLE0 site, GATA-3 but not GATA-1 binds
to the GATA motif and regulates the expression of IL-5 in the
combination with other factors, AP-1 and Elf-1 (24).
In mast cells, IL-4 gene expression is regulated by two GATA family
proteins, GATA-1 and GATA-2, and PU.1, which belongs to Ets family
(52). The expression of mast cell carboxypeptidase A is
known to be regulated predominantly by GATA-1 in mast cells
(53). However, in a mast cell line, P815, which is
negative in both FcRI (2) and mast cell
carboxypeptidase A, the expression of GATA-1 was not observed (Table I). This also suggests that GATA-1 is essential for the expression of
FcRI -chain and plays a crucial role in the expression of certain
genes in mast cells.
The Ets motif was found in the FcRI -chain genes of mouse, rat,
and human (Fig. 7). Furthermore, the sequence is also present in other
Fc receptor genes, suggesting an indispensable role of the sequence in
the regulation of the expression of Fc receptors in myeloid cells
(54, 55). The fact that the motif is recognized by Elf-1
in this study indicates that all the Ets sequences in other Fc receptor
genes might be also recognized by Elf-1 in each myeloid cell. The
further involvement of Elf-1 in other Fc receptor genes remains to be
analyzed.
Here, we have revealed a part of the cell-specific transcription
mechanisms of the FcRI -chain, mediated by two transcription
factors, Elf-1 and GATA-1. Recently, the expression of FcRI were
reported to be up-regulated by IL-4 (14, 15, 16, 17), which was
known to transfer the signal to the STAT6 motif. For better
understanding of the expression mechanisms of FcRI -chain, it
would be necessary to examine whether the functional STAT6 motifs exist
in the FcRI -chain gene. The present study has become the first
step to elucidate the expression mechanism of FcRI.
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Acknowledgments |
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Footnotes |
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2 Abbreviations used in this paper: FcRI, high-affinity IgE receptor; CLE0, conserved lymphokine element 0.
Received for publication December 22, 1998. Accepted for publication April 27, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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  S. Kanada, N. Nakano, D. P. Potaczek, K. Maeda, N. Shimokawa, Y. Niwa, T. Fukai, M. Sanak, A. Szczeklik, H. Yagita, et al. Two Different Transcription Factors Discriminate the -315C>T Polymorphism of the Fc{epsilon}RI{alpha} Gene: Binding of Sp1 to -315C and of a High Mobility Group-Related Molecule to -315T J. Immunol., June 15, 2008; 180(12): 8204 - 8210. [Abstract] [Full Text] [PDF]
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 F. Martelli, B. Ghinassi, R. Lorenzini, A. M. Vannucchi, R. A. Rana, M. Nishikawa, S. Partamian, G. Migliaccio, and A. R. Migliaccio Thrombopoietin Inhibits Murine Mast Cell Differentiation Stem Cells, April 1, 2008; 26(4): 912 - 919. [Abstract] [Full Text] [PDF]
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 N. Nakano, C. Nishiyama, S. Kanada, Y. Niwa, N. Shimokawa, H. Ushio, M. Nishiyama, K. Okumura, and H. Ogawa Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections Blood, June 1, 2007; 109(11): 4846 - 4855. [Abstract] [Full Text] [PDF]
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A. Masuda, K. Hashimoto, T. Yokoi, T. Doi, T. Kodama, H. Kume, K. Ohno, and T. Matsuguchi Essential Role of GATA Transcriptional Factors in the Activation of Mast Cells J. Immunol., January 1, 2007; 178(1): 360 - 368. [Abstract] [Full Text] [PDF]
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K. Maeda, C. Nishiyama, T. Tokura, H. Nakano, S. Kanada, M. Nishiyama, K. Okumura, and H. Ogawa FOG-1 represses GATA-1-dependent Fc{epsilon}RI beta-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice Blood, July 1, 2006; 108(1): 262 - 269. [Abstract] [Full Text] [PDF]
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 C. Nishiyama, T. Ito, M. Nishiyama, S. Masaki, K. Maeda, N. Nakano, W. Ng, K. Fukuyama, M. Yamamoto, K. Okumura, et al. GATA-1 is required for expression of Fc{varepsilon}RI on mast cells: analysis of mast cells derived from GATA-1 knockdown mouse bone marrow Int. Immunol., July 1, 2005; 17(7): 847 - 856. [Abstract] [Full Text] [PDF]
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D. MacGLASHAN JR. IgE and Fc{epsilon}RI Regulation Ann. N.Y. Acad. Sci., June 1, 2005; 1050(1): 73 - 88. [Abstract] [Full Text] [PDF]
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C. Nishiyama, Y. Akizawa, M. Nishiyama, T. Tokura, H. Kawada, K. Mitsuishi, M. Hasegawa, T. Ito, N. Nakano, A. Okamoto, et al. Polymorphisms in the Fc{epsilon}RI{beta} Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between Fc{epsilon}RI{beta} and Atopy J. Immunol., November 15, 2004; 173(10): 6458 - 6464. [Abstract] [Full Text] [PDF]
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A. Masuda, Y. Yoshikai, H. Kume, and T. Matsuguchi The Interaction between GATA Proteins and Activator Protein-1 Promotes the Transcription of IL-13 in Mast Cells J. Immunol., November 1, 2004; 173(9): 5564 - 5573. [Abstract] [Full Text] [PDF]
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