The CCAAT/enhancer-binding protein trans-activates the human cholesteryl ester transfer protein gene promoter.
The plasma cholesteryl ester transfer protein (CETP), primarily synthesized in the liver of several species, is expressed at very low levels in a number of transformed human liver cell lines. The human CETP gene promoter contains a sequence that closely resembles the binding site for the transcription factor CCAAT/enhancer-binding protein (C/EBP). This site is capable of binding C/EBP, as shown by electrophoretic mobility shift and DNase I footprint analyses. Transient expression of the bacterial chloramphenicol acetyltransferase gene under the control of the human CETP gene promotor gave low activities in the human hepatoma cell line, HepG2. However, in the presence of C/EBP, CAT activity was markedly elevated indicating that CETP gene promoter activity was enhanced. In primary cultures of isolated hepatocytes, CETP mRNA was lost rapidly and in parallel with the C/EBP mRNA. C/EBP may play an important role in the proper maintenance of CETP gene promoter activity, and its low levels in proliferating or cultured cells may account for the low level of the CETP gene expression in immortalized human liver cell lines or cultured hepatocytes.
Agellon
L B
LB
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Zhang
P
P
Jiang
X C
XC
Mendelsohn
L
L
Tall
A R
AR
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006023:Glycoproteins; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors