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Department of Biochemistry (T.S.), Department of Obstetrics and Gynecology (S.F.), Hokkaido University School of Medicine, Sapporo, Hokkaido 060-8638, Japan; and Division of Virology of the National Cancer Center Research Institute (M.S.), Tsukiji, Tokyo 104-0045, Japan
Address all correspondence and requests for reprints to: Teruo Sugawara, Department of Biochemistry, Hokkaido University School of Medicine, Kita-ku, Kita 15, Nishi 7, Sapporo 060-8638, Japan. E-mail: terusuga{at}med.hokudai.ac.jp
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The tropic hormones ACTH, LH, and FSH stimulate steroid production by their respective target cells (6). When a tropic hormone binds to its cognate receptor, intracellular cAMP levels increase via a G protein-coupled mechanism, and cAMP-dependent protein kinase [protein kinase A (PKA)] is activated (7). Steroid production increases within 30 min of tropic hormone stimulation (8). This acute steroidogenic response is associated with protein phosphorylation. StAR has PKA consensus phosphorylation sites that are important for StAR function (9). There is a second pathway that induces an increase in steroid hormone production, which can last several hours to several days. This pathway involves a mechanism that increases transcription of genes encoding the enzymes of steroid biosynthesis (2). StAR expression is restricted to steroid-producing cells of the adrenal gland, testis, and ovary; and StAR expression is increased by cAMP (10). The results of nuclear run-on assays revealed that cAMP regulates the abundance of StAR messenger RNA at the transcriptional level (11). The cAMP-induced increase in StAR expression is blocked by cycloheximide, an inhibitor of protein synthesis (11, 12), suggesting that newly synthesized proteins are required for cAMP-stimulated StAR gene transcription. The human, mouse, and porcine StAR genes each contain steroidogenic factor 1 (SF-1) binding sites in their promoters (13, 14, 15, 16). SF-1 is an orphan nuclear receptor whose ligand has not been identified (17), although it has been reported that oxysterols might be SF-1-activating ligands (18). Oxysterols have cell-specific effects on SF-1-dependent transactivation, perhaps attributable to cell-specific pathways of oxysterol metabolism (19). SF-1, which has also been named Ad4BP, plays a major role in regulating the expression of steroidogenic P450 enzymes (20, 21, 22). SF-1 also plays a role in controlling the basal and cAMP-stimulated expression of the human StAR gene (15). The 1.3-kb human StAR promoter has three SF-1 binding sites: a distal site (-926 to -918), a middle site (-105 to -96), and an SF-1 binding site (-43 to -36) near the TATA box (23). The distal SF-1 consensus-binding site is important for basal activity, whereas the middle and TATA-box sites are important for basal and cAMP-stimulated promoter activity (23). The human StAR promoter also has two consensus transcription factor Sp1 site sequences near the more distal SF-1 binding sites (15). Sp1 mediates cAMP-dependent transcription of the P450scc gene (24), raising the possibility that it participates in the cAMP regulation of StAR gene expression. However, the mechanism by which Sp1 mediates cAMP activation of transcription has not been elucidated. In the present study, we clarified the mechanism by which SF-1 and Sp1 act cooperatively on the human StAR promoter.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Plasmid pVP16-SF-1 was constructed by inserting the EcoRI/SalI fragment from mouse SF-1 cDNA into the pVP16 vector, which has an activation domain (AD) derived from the VP16 protein of herpes simplex virus. To produce plasmid pM-Sp1, the fragment including the entire Sp1 coding region was amplified by PCR from Sp1 cDNA into the pM vector, which has a GAL4 DNA-binding domain (DNA-BD). Furthermore, we prepared the reverse combinations, constructing pVP16-Sp1 by inserting the EcoRI fragment of the amplified Sp1 coding sequence into the pVP16 vector. To produce plasmid pM-SF-1, the EcoRI fragment from mouse SF-1 cDNA was cloned into the pM vector. pG5CAT (CLONTECH Laboratories, Inc.) and pG5luc (Promega Corp.) contain the CAT gene or the luciferase gene, respectively, as a reporter. The plasmids were prepared for transfection studies using the Maxiprep system (QIAGEN, Hilden, Germany).
Cell culture
The mouse Y-1 adrenal tumor cells and COS-1 cells were obtained
from RIKEN Cell BANK (Tsukuba, Japan). The human adrenocortical
carcinoma H295R cells were a gift from Dr. Mitsuhiro Okamoto, Osaka
University Medical School (Osaka, Japan). Drosophila
melanogaster Schneider’s Drosophila line 2 cells were a gift from
Dr. Masamitsu Yamaguchi, Aichi Cancer Center Research Institute
(Nagoya, Japan). Cells were grown in 35-mm plastic dishes. The Y-1
cells and COS-1 cells were cultured with DMEM supplemented with 10%
FCS and 50 µg/ml of gentamycin. H295R cells were grown in DMEM/F12
containing 2% ULTROSER G (BioSepra, Cergy-Pontoise, France) and 1%
ITS Premix (Becton Dickinson and Co., Franklin Lakes,
NJ). Schneider’s Drosophila cells were cultured at 20 C in
Schneider’s Droshohila medium (Life Technologies, Inc./BRL, Washington, DC) supplemented with
10% FCS.
Transfection and luciferase assays
Cultures at 40–60% confluence were first washed with
serum-free medium. Next, 0.5 ml serum-free medium containing either
pGL2 plasmids and pCH110 with 3 µl Tfx-20
(Promega Corp.) per 1 µg DNA or Sp1 or SF-1 expression
plasmids, were added. After incubation for 1 h, 1.5 ml of the
medium, supplemented with 10% FCS or 2% ULTROSER G and 1% ITS
Premix, was added. Cells were harvested 48 h after transfection.
Some dishes were treated with 8-Br-cAMP (1 mM) during the
final 24 h of culture.
Cells were harvested 48 h after transfection, and extracts were made in lysis buffer (Promega Corp.). One aliquot (100 µl out of 400 µl total extract vol) was used for the luciferase assay (Luciferase Assay System, Promega Corp.), and 150 µl was used for the ß-galactosidase assay (ß-Galactosidase Enzyme Assay System, Promega Corp.). The so-called blank luciferase value was measured in extracts of untransfected cells. The luciferase assay results were normalized to ß-galactosidase activity to compensate for variations in transfection efficiency. Each treatment group contained triplicate cultures, and each experiment was repeated three or four times.
Preparation of SF-1-GST fusion protein
The murine SF-1-GST fusion protein construct, provided by Dr.
Keith Parker, was expressed in bacteria (25) and was used for
electrophoretic mobility shift assays (EMSAs) or
coimmunoprecipitation.
EMSAs
An oligonucleotide that contained both consensus Sp1 and SF-1
sites (-172 to -85) was prepared by PCR using the following
oligonucleotides: 5'-CCCCTGCACCCTCCCCCGCCCCAAG-3' and
5'-CAAAGGAAGGGGTCAAGGATAGAGCGATT-3'. A -172 to -85 probe with a
mutated Sp1 site was also prepared using the following
oligonucleotides: 5'-CCCCTGCACCCTCCCAAGCCCCAAG-3' and
5'-CAAAGGAAGGGGTCAAGGATAGAGCGATT-3'. The SF-1 binding site was analyzed
using a double-stranded oligonucleotide probe produced from the
following oligonucleotides: 5'-AATCGCTCTATCCTTGACCCCTTCCTTTG-3' and
5'-GCAAAGGAAGGGGTCAAGGATAGAGCGAT-3'. The PCR products and
double-stranded synthetic oligonucleotides were labeled using T4
polynucleotide kinase and [
32P]ATP.
EMSA was carried out with 1–3 µl of (0.1 µg/µl) SF-1 GST fusion
protein preparation and recombinant Sp1 (Promega Corp.),
in a vol of 10 µl with 2 x 105 cpm
32P-labeled probe, and gel shift binding buffer
(Promega Corp.) according to the supplier’s protocol. In
some experiments, 1 µl antibody to mouse SF-1 (26), Sp1 antibody
(Santa Cruz Biotechnology, Inc., Santa Cruz, CA),
or nonimmune serum was added to the mixture, 10 min before the addition
of the labeled probe. The reaction mixtures were incubated at room
temperature for 30 min. They were then subjected to 4% PAGE at 150 V
for 2 h and to autoradiography.
Cross-linking experiment and coimmunoprecipitation
Recombinant Sp1 was incubated with GST or GST-SF-1. The reaction
mixture was diluted with binding buffer (20 mM HEPES, 5%
glycerol, 100 mM KCl, 5 mM
MgCl2, 0.5 mM dithiothreitol, 1
mM EDTA in a final vol of 25 µl) and cross-linked with an
irreversible cross-linking agent (2 mM disuccinimidyl
suberate) for 7 min at 14 C, then quenched by the addition of 1 M
ammonium acetate to 5 mM final. The cross-linked products
were fractionated on a 12% SDS polyacrylamide gel and subjected to
Western blot analysis with Sp1 or SF-1 antibody.
Coimmunoprecipitations were performed using in vitro translated protein, as described by Porter (27). The pCMV SF-1 plasmid was used to generate radiolabeled SF-1 in the TnT T7-coupled reticulocyte lysate system (Promega Corp.). 35S-labeled SF-1 was incubated with recombinant Sp1. The reaction mixture was diluted with binding buffer and cross-linked with a reversible cross-linking agent [5 mM dithiobis(succinimidyl propionate)] for 1 h at 25 C, then quenched with 0.22 M lysine, as described by Lin (28). Radioimmunoprecipitation was carried out by adding 500 µl RIPA buffer (PBS, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, 10 mg/ml phenylmethylsulfonyl fluoride, 30 µg/ml aprotinin, and 10 µg/ml sodium orthovanadate) and 1 µl of antisera. After incubating for 1 h at 4 C, 20 µl Protein G Sepharose 4FF (Amersham Pharmacia Biotech) was added, and the mixture was incubated for 1 h at 4 C. The bound complex was then washed four times with RIPA buffer containing 2 M urea. The precipitated proteins were eluted with 2x SDS sample buffer to reverse the cross-links, resolved on a 12% SDS polyacrylamide gel, dried, and visualized by autoradiography.
The two-hybrid assay
Y-1 cells or COS-1 cells were collected after 48 h of
transfection with 1.5 µg of the pG5CAT reporter plasmid, 1.5 µg of
a pM-Sp1 (GAL4-Sp1) expression plasmid, 0.25 µg of a
pVP16-SF-1 (VP16-SF-1) expression plasmid, and 0.1 µg PCH110. CAT
assays were performed using the CAT ELISA Kit (Roche Molecular Biochemicals, Mannheim, Germany). A luciferase reporter
assay was used for the reversed constructs (Sp1 fused to VP16 AD and
SF-1 fused to GAL4 DB). Cells were transfected with 0.25 µg of the
pG5luc plasmid, 1 µg pM SF-1
(GAL4-SF-1), 25 ng pVP-Sp1 (VP16-Sp1), and 0.25 µg PCH110. The assay
results were normalized to ß-galactosidase activity to compensate for
variations in transfection efficiency. Each experiment was repeated at
least three times.
Data analysis
Values are presented as means ± SE.
Significance between experimental values was determined by Student’s
unpaired t test. P < 0.05 was taken as the
level of significance.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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. The human 1.3-kb StAR promoter, as
well as various deletion constructs, were transfected into mouse Y-1
cells and human H295R cells, which express endogenous SF-1. The 1.3-kb
StAR promoter contains two Sp1 sites, one SF-1 consensus binding site,
and two SF-1-like binding sites (-105 to -96 and -43 to -36). One
or more of these binding sites were removed in the deletion constructs.
pGL2 StAR, which was constructed from the -235 to
+39 fragment, contains two SF-1 binding sites (-105 to -96 and -43
to -36) and an Sp1 consensus binding site (-157 to -151). This
promoter fragment was as active as the human 1.3-kb StAR promoter in
both mouse Y-1 cells and human H295R cells. In H295R cells,
cAMP-stimulated promoter activity was particularly conspicuous in this
-235 to +39 fragment. Basal and cAMP-stimulated promoter activities of
the construct that lacked the Sp1 binding site,
pGL2
-150/+39, were reduced by 47% and 55%
of the respective values observed with the 1.3-kb StAR promoter in Y-1
cells (Fig. 2A). Based and
cAMP-stimulated promoter activity of the construct was also reduced by
34% and 42%, respectively, in the context of H295R cells (Fig. 2B).
In the construct that lacked both the Sp1(-157 to -151) and SF-1
binding sites(-105 to -96), pGL2-85/+39,
basal, and cAMP-stimulated promoter activities were ablated both in Y-1
cells and H295R cells.
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).
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), and COS-1 cells, which do not
express endogenous SF-1 (Fig. 4B); and the promoter activities of
PGL2 StAR and pGL2Sp1M
constructs were compared. Although COS-1 cells were not responsive to
exogenous cAMP without the transfected SF-1 expression plasmid, the
introduction of exogenous SF-1 resulted in a dose-dependent increase in
human StAR promoter activity both in Y-1 cells and COS-1 cells.
However, the pGL2Sp1M promoter construct did not
respond to exogenous SF-1.
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). Sp1 or SF-1
expression plasmids were also transfected into COS-1 cells, which do
not express endogenous SF-1 expression, and Schneider’s cells, which
do not express endogenous Sp1 expression. When transfected with the
SF-1 expression plasmid, COS-1 cells were responsive to exogenous cAMP.
When COS-1 cells were transfected with only Sp1 plasmids, basal and
cAMP-stimulated promoter activities increased with increasing amounts
of the Sp1 expression plasmid, but exogenous Sp1 did not change cAMP
induction of the human StAR promoter (Fig. 5B). Even though the SF-1
expression plasmid was transfected, StAR promoter activity on
Schneider’s cells was not responsive to exogenous cAMP. StAR promoter
activity was not increased when Schneider’s cells transfected with the
Sp1 expression plasmid (Fig. 5C). Moreover, cotransfection with Sp1 and
SF-1 expression plasmids did not increase basal and cAMP-stimulated
promoter activities. These experimental results suggest that Sp-1
interacts functionally with SF-1 in the control of the human StAR gene
in the context of mammalian cells.
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). We prepared a probe with a
mutated Sp1 site and an SF-1 binding site. GST-SF-1 formed a
protein-DNA complex, but recombinant Sp1 did not form a protein-DNA
complex. When SF-1 and Sp1 were incubated together, neither an Sp1-DNA
complex nor a third complex were formed (Fig. 6B). Therefore, the third
band seems to be an SF-1-Sp1-DNA complex.
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). We also examined the binding of
GST-SF-1 fusion protein to the probe in the presence of recombinant
Sp1. Two bands representing DNA complexes were formed. To identify the
proteins in these complexes, the SF-1 antibody or Sp1 antibody was
added to the EMSA reaction mixtures. The GST-SF-1-DNA complex was
supershifted when the SF-1 antibody was added, and the Sp1-GST-SF-1-DNA
complex disappeared when the Sp1 antibody was added. Thus, one complex
was formed by GST-SF-1-DNA confirmed with the SF-1 antibody. The other
was a GST-SF-1-Sp1-DNA complex, which was inhibited by adding the Sp1
antibody (Fig. 7B). These EMSA results suggest that Sp1 and SF-1
interact with each other in vitro to form complexes with
DNA.
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). To corroborate the
physical interaction, coimmunoprecipitations were employed using
in vitro translated [35S]SF-1
protein and recombinant Sp1. [35S]SF-1 and Sp1
were incubated and cross-linked with dithiobis[succinimidyl
propionate], a bifunctional, reversible cross-linker. The protein
complexes were immunoprecipitated with Sp1 Ab, SF-1 antiserum, or
preimmune serum and protein G-Sepharose. Washed beads were boiled in
SDS sample buffer to reverse the cross-links. As indicated in Fig. 8B, 35S-labeled SF-1 and Sp1 complexes were
precipitated with the Sp1 antibody, and SF-1 interacted with Sp1
prebound to protein G Sepharose.
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; A,
B, and C). In this assay, we employed pM-Sp1, which
expresses Sp1 fused to the GAL4 DNA-BD, and pVP16-SF-1, a fusion
construct of SF-1 to AD derived from the VP16 protein of herpes simplex
virus. We also prepared reverse combinations in which Sp1 was fused to
VP16 AD (pVP16-Sp1) and SF-1 was fused to GAL4 DB (pM-Sp1).
pG5CAT and pG5luc were the reporter vectors that contain the
CAT or luciferase gene downstream of five consensus GAL4 binding sites.
The empty vectors, GAL4 DNA-BD (pM) and AD
(pVP16), did not activate the reporter genes. Cotransfection of GAL4
DNA-BD (pM) and AD-SF-1 (pVP16-SF-1), AD-Sp1
(pVP16-Sp1), or GAL4 DNA-BD-Sp1 (pM-Sp1), GAL4
DNA-BD-SF-1, and AD (pVP16) did not increase reporter activity.
However, the GAL4 DNA-BD-Sp1 (pM-Sp1) and AD-SF-1
(pVP16-SF-1) fusion proteins induced 19-fold greater activation of the
promoter, compared with the activity observed when the
pM and pVP16 vectors were cotransfected into Y-1
cells (Fig. 9A). The switched domain constructs,
pM-SF-1 and pVP16-Sp1, also activated the
reporter in Y-1 cells (Fig. 9B). Cotransfection with
pM-SF-1 and pVP16-Sp1 increased promoter activity
by 3.5-fold in COS-1 cells (Fig. 9C). These findings reflected the
interaction between Sp1 and SF-1 in vivo.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Deletion analysis and mutation analysis of the human StAR promoter demonstrated that Sp1 has an effect on promoter activity in conjunction with SF-1. Overexpression of SF-1 in Y-1 cells and COS-1 cells increased StAR promoter activity. StAR promoter activity in Schneider’s cells was not responsive to exogenous Sp1. The failure to observe a response to exogenous Sp1 may reflect the absence of other transcription factors, coactivators, or corepressors required for the regulation of the StAR promoter in these insect cells. Thus, productive SF-1-Sp1 interactions may require a mammalian cell host. With a mutation in the Sp1 binding site, SF-1 induced a smaller increase in StAR promoter activity. These findings coincide with the results of deletion and mutation analysis carried out in the absence of exogenous SF-1 and Sp1.
The EMSAs for formation of SF-1-Sp1-DNA complexes, using an oligonucleotide probe incorporating the -172 to -85 sequence, indicated that SF-1 and Sp1 bind to their respective sites and interact with each other to control the human StAR promoter. EMSAs, using a probe containing only an SF-1 site, also indicated an interaction between SF-1 and Sp1. The fact that SF-1 and Sp1 were coimmunoprecipitated together supports the notion that Sp1 and SF-1 interact directly with each other. Moreover, in the two-hybrid assay, Sp1 fused to Gal4 BD and SF-1 fused to VP 16 AD, and the switched domains (Sp1 fused to VP16 AD and SF-1 fused to Gal4 BD) activated the reporter constructs, indicating an interaction between these transcription factors in an intact cell system.
The ubiquitous transcription factor Sp1 adjusts the promoter activity of various genes, and Sp1 can interact with other transcription factors to achieve this modulation (29, 30). We have demonstrated the interaction between Sp1 and SF-1 on the human StAR promoter. Other investigators have suggested an interaction between Sp1 and SF-1 on steroidogenic enzyme gene promoters (24). Although Sp1 and SF-1 interact with each other and cooperate to regulate the basal activity of the human StAR promoter, these interactions have only a small influence on cAMP responses. Other proteins, including CBP (31), C/EBPß (32, 33), and coactivators or possibly corepressors, may combine with SF-1 (34, 35) and Sp1 to amplify the cAMP response (36). It has recently been shown that C/EBPß participates in the cAMP regulation of StAR gene transcription (32). Sp1 and C/EBPß can work in conjunction to active the CYP2D5 gene by stabilizing binding or increasing the affinity of C/EBPß (37). Thus, Sp1 and SF-1 may interact with C/EBPß to control the human StAR promoter activity.
Steroid hormone biosynthesis is controlled by ACTH, LH, and FSH, which increase intracellular cAMP levels, which, in turn, activates PKA. The increase in StAR expression resulting from increases in cAMP could involve PKA-mediated phosphorylation of transcription factors regulating the StAR promoter. Sp1 does not have consensus motifs for PKA phosphorylation (38). However, SF-1 contains a PKA phosphorylation site and can be phosphorylated by PKA (22, 39). It remains to be determined whether cAMP-induced phosphorylation of SF-1 alters its activities on the StAR promoter and its ability to interact with Sp1.
In conclusion, our studies have provided strong evidence of interaction between Sp1, a global transcription factor, and SF-1 in the regulation of human StAR gene transcription. This interaction provides a new framework for understanding the regulation of human StAR gene expression.
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Acknowledgments |
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Footnotes |
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Received October 20, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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V. Sriraman and J. S. Richards Cathepsin L Gene Expression and Promoter Activation in Rodent Granulosa Cells Endocrinology, February 1, 2004; 145(2): 582 - 591. [Abstract] [Full Text] [PDF]
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B. Borud, G. Mellgren, J. Lund, and M. Bakke Cloning and Characterization of a Novel Zinc Finger Protein that Modulates the Transcriptional Activity of Nuclear Receptors Mol. Endocrinol., November 1, 2003; 17(11): 2303 - 2319. [Abstract] [Full Text] [PDF]
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T. Sugawara, H. Shimizu, N. Hoshi, A. Nakajima, and S. Fujimoto Steroidogenic Acute Regulatory Protein-binding Protein Cloned by a Yeast Two-hybrid System J. Biol. Chem., October 24, 2003; 278(43): 42487 - 42494. [Abstract] [Full Text] [PDF]
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H. S. Sun, K.-Y. Hsiao, C.-C. Hsu, M.-H. Wu, and S.-J. Tsai Transactivation of Steroidogenic Acute Regulatory Protein in Human Endometriotic Stromal Cells Is Mediated by the Prostaglandin EP2 Receptor Endocrinology, September 1, 2003; 144(9): 3934 - 3942. [Abstract] [Full Text] [PDF]
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S. B. R. Jacobs, D. Coss, S. M. McGillivray, and P. L. Mellon Nuclear Factor Y and Steroidogenic Factor 1 Physically and Functionally Interact to Contribute to Cell-Specific Expression of the Mouse Follicle-Stimulating Hormone-{beta} Gene Mol. Endocrinol., August 1, 2003; 17(8): 1470 - 1483. [Abstract] [Full Text] [PDF]
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A. K. Ghosh, R. Steele, and R. B. Ray Modulation of Human Luteinizing Hormone {beta} Gene Transcription by MIP-2A J. Biol. Chem., June 20, 2003; 278(26): 24033 - 24038. [Abstract] [Full Text] [PDF]
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V. Sriraman, S. C. Sharma, and J. S. Richards Transactivation of the Progesterone Receptor Gene in Granulosa Cells: Evidence that Sp1/Sp3 Binding Sites in the Proximal Promoter Play a Key Role in Luteinizing Hormone Inducibility Mol. Endocrinol., March 1, 2003; 17(3): 436 - 449. [Abstract] [Full Text] [PDF]
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H. Osman, C. Murigande, A. Nadakal, and A. M. Capponi Repression of DAX-1 and Induction of SF-1 Expression. TWO MECHANISMS CONTRIBUTING TO THE ACTIVATION OF ALDOSTERONE BIOSYNTHESIS IN ADRENAL GLOMERULOSA CELLS J. Biol. Chem., October 18, 2002; 277(43): 41259 - 41267. [Abstract] [Full Text] [PDF]
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 J. von Hofsten, J. Karlsson, I. Jones, and P.-E. Olsson Expression and Regulation of Fushi Tarazu Factor-1 and Steroidogenic Genes During Reproduction in Arctic Char (Salvelinus alpinus) Biol Reprod, October 1, 2002; 67(4): 1297 - 1304. [Abstract] [Full Text] [PDF]
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M. Abdelrahim, I. Samudio, R. Smith III, R. Burghardt, and S. Safe Small Inhibitory RNA Duplexes for Sp1 mRNA Block Basal and Estrogen-induced Gene Expression and Cell Cycle Progression in MCF-7 Breast Cancer Cells J. Biol. Chem., August 2, 2002; 277(32): 28815 - 28822. [Abstract] [Full Text] [PDF]
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P. R. Manna, M. T. Dyson, D. W. Eubank, B. J. Clark, E. Lalli, P. Sassone-Corsi, A. J. Zeleznik, and D. M. Stocco Regulation of Steroidogenesis and the Steroidogenic Acute Regulatory Protein by a Member of the cAMP Response-Element Binding Protein Family Mol. Endocrinol., January 1, 2002; 16(1): 184 - 199. [Abstract] [Full Text] [PDF]
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L. M. Salvador, Y. Park, J. Cottom, E. T. Maizels, J. C. R. Jones, R. V. Schillace, D. W. Carr, P. Cheung, C. D. Allis, J. L. Jameson, et al. Follicle-stimulating Hormone Stimulates Protein Kinase A-mediated Histone H3 Phosphorylation and Acetylation Leading to Select Gene Activation in Ovarian Granulosa Cells J. Biol. Chem., October 19, 2001; 276(43): 40146 - 40155. [Abstract] [Full Text] [PDF]
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T. Sugawara, S. Abe, N. Sakuragi, Y. Fujimoto, E. Nomura, K. Fujieda, M. Saito, and S. Fujimoto RIP 140 Modulates Transcription of the Steroidogenic Acute Regulatory Protein Gene through Interactions with Both SF-1 and DAX-1 Endocrinology, August 1, 2001; 142(8): 3570 - 3577. [Abstract] [Full Text] [PDF]
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W. K. Shea-Eaton, M. J. Trinidad, D. Lopez, A. Nackley, and M. P. McLean Sterol Regulatory Element Binding Protein-1a Regulation of the Steroidogenic Acute Regulatory Protein Gene Endocrinology, April 1, 2001; 142(4): 1525 - 1533. [Abstract] [Full Text]
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L. K. Christenson, R. L. Stouffer, and J. F. Strauss III Quantitative Analysis of the Hormone-induced Hyperacetylation of Histone H3 Associated with the Steroidogenic Acute Regulatory Protein Gene Promoter J. Biol. Chem., July 13, 2001; 276(29): 27392 - 27399. [Abstract] [Full Text] [PDF]
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