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J Biol Chem, Vol. 274, Issue 25, 17987-17996, June 18, 1999
From the Department of Biological Chemistry, Alexander Silberman
Institute of Life Sciences, The Hebrew University of Jerusalem,
Jerusalem 91904, Israel
Steroidogenic acute regulatory protein (StAR) is
a vital accessory protein required for biosynthesis of steroid hormones
from cholesterol. The present study shows that in primary granulosa cells from prepubertal rat ovary, StAR transcript and protein are
acutely induced by gonadotropin (FSH). To determine the sequence elements required for hormone inducibility of the StAR promoter, truncated regions of the
CCAAT Enhancer-binding Protein
and GATA-4 Binding Regions
within the Promoter of the Steroidogenic Acute Regulatory Protein
(StAR) Gene Are Required for Transcription in Rat Ovarian Cells
1002/+6 sequence of the mouse gene were ligated to pCAT-Basic plasmid and transfected by electroporation to
freshly prepared cells. FSH inducibility determined over a 6-h
incubation was 10-40-fold above basal levels of chloramphenicol acetyltransferase activity. These functional studies, supported by electrophoretic mobility shift assays indicated that two sites were
sufficient for transcription of the StAR promoter constructs: a
non-consensus binding sequence (81/72) for CCAAT enhancer-binding protein 
(C/EBP) and a consensus motif for GATA-4 binding
(61/66). Western analyses showed that GATA-4 is constitutively
expressed in the granulosa cells, while all isoforms of C/EBP were
markedly inducible by FSH. Site-directed mutations of both binding
sequences practically ablated both basal and hormone-driven
chloramphenicol acetyltransferase activities to less than 5% of the
parental 96/+6 construct. Unlike earlier notions, elimination of
potential binding sites for steroidogenic factor-1, a well known
tissue-specific transcription factor, did not impair StAR
transcription. Consequently, we propose that C/EBP and GATA-4
represent a novel combination of transcription factors capable of
conferring an acute response to hormones upon their concomitant binding
to the StAR promoter.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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 E. Querfurth, M. Schuster, H. Kulessa, J. D. Crispino, G. Döderlein, S. H. Orkin, T. Graf, and C. Nerlov Antagonism between C/EBPbeta and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors Genes & Dev., October 1, 2000; 14(19): 2515 - 2525. [Abstract] [Full Text]
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M. P. E. Laitinen, M. Anttonen, I. Ketola, D. B. Wilson, O. Ritvos, R. Butzow, and M. Heikinheimo Transcription Factors GATA-4 and GATA-6 and a GATA Family Cofactor, FOG-2, Are Expressed in Human Ovary and Sex Cord-Derived Ovarian Tumors J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3476 - 3483. [Abstract] [Full Text]
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 M. Shapira, I. Tur-Kaspa, L. Bosgraaf, N. Livni, A. D. Grant, D. Grisaru, M. Korner, R. P. Ebstein, and H. Soreq A transcription-activating polymorphism in the ACHE promoter associated with acute sensitivity to anti-acetylcholinesterases Hum. Mol. Genet., May 22, 2000; 9(9): 1273 - 1281. [Abstract] [Full Text] [PDF]
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C. R. Wooton-Kee and B. J. Clark Steroidogenic Factor-1 Influences Protein-Deoxyribonucleic Acid Interactions within the Cyclic Adenosine 3',5'-Monophosphate-Responsive Regions of the Murine Steroidogenic Acute Regulatory Protein Gene Endocrinology, April 1, 2000; 141(4): 1345 - 1355. [Abstract] [Full Text] [PDF]
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M. Niehof, K. Streetz, T. Rakemann, S. C. Bischoff, M. P. Manns, F. Horn, and C. Trautwein Interleukin-6-induced Tethering of STAT3 to the LAP/C/EBPbeta Promoter Suggests a New Mechanism of Transcriptional Regulation by STAT3 J. Biol. Chem., March 16, 2001; 276(12): 9016 - 9027. [Abstract] [Full Text] [PDF]
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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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J. D. Molkentin The Zinc Finger-containing Transcription Factors GATA-4, -5, and -6. UBIQUITOUSLY EXPRESSED REGULATORS OF TISSUE-SPECIFIC GENE EXPRESSION J. Biol. Chem., December 8, 2000; 275(50): 38949 - 38952. [Full Text] [PDF]
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