TY - JOUR
T1 - Repressive effect of Sp1 on the C/EBPα gene promoter
T2 - Role in adipocyte differentiation
AU - Tang, Qi Qun
AU - Jiang, Man Shiow
AU - Lane, M. Daniel
PY - 1999/7
Y1 - 1999/7
N2 - Expression of C/EBPα is required for differentiation of 3T3-L1 preadipocytes into adipocytes. Previous investigations indicated that transcription of the C/EBPα gene is sequentially activated during differentiation, initially by C/EBPβ and C/EBPδ and later by C/EBPα (autoactivation). These events are mediated by a C/EBP regulatory element in the promoter of the C/EBPα gene. This article presents evidence that members of the Sp family, notably Sp1, act repressively on the C/EBPα 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/EBPα 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/EBPβ and/or C/EBPδ to the C/EBP regulatory element and, thereby, derepression of the C/EBPα gene.
AB - Expression of C/EBPα is required for differentiation of 3T3-L1 preadipocytes into adipocytes. Previous investigations indicated that transcription of the C/EBPα gene is sequentially activated during differentiation, initially by C/EBPβ and C/EBPδ and later by C/EBPα (autoactivation). These events are mediated by a C/EBP regulatory element in the promoter of the C/EBPα gene. This article presents evidence that members of the Sp family, notably Sp1, act repressively on the C/EBPα 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/EBPα 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/EBPβ and/or C/EBPδ to the C/EBP regulatory element and, thereby, derepression of the C/EBPα gene.
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M3 - Article
C2 - 10373535
AN - SCOPUS:0033059674
SN - 0270-7306
VL - 19
SP - 4855
EP - 4865
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 7
ER -