Molecular and Cellular Biology, July 1999, p. 4855-4865, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Gene
Promoter: Role in Adipocyte Differentiation
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Received 22 October 1998/Returned for modification 6 January 1999/Accepted 21 April 1999
Expression of C/EBP
is required for differentiation of 3T3-L1
preadipocytes into adipocytes. Previous investigations indicated that
transcription of the C/EBP
gene is sequentially activated during
differentiation, initially by C/EBP
and C/EBP
and later by
C/EBP
(autoactivation). These events are mediated by a C/EBP regulatory element in the promoter of the C/EBP
gene. This article presents evidence that members of the Sp family, notably Sp1, act
repressively on the C/EBP
promoter prior to the induction of
differentiation. Sp1 was shown to bind to a GC box at the 5' end of the
C/EBP regulatory element in the C/EBP
promoter and, in so doing, to
competitively prevent binding to and transactivation of the promoter by
the C/EBPs. One of the differentiation inducers methylisobutylxanthine
(a cAMP phosphodiesterase inhibitor) or Forskolin, both of which
increase the cellular cAMP level, causes down-regulation of Sp1. This
decrease in Sp1 level early in the differentiation program appears to
facilitate access of C/EBP
and/or C/EBP
to the C/EBP regulatory
element and, thereby, derepression of the C/EBP
gene.
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