TY - JOUR
T1 - 42 bp element from LDL receptor gene confers end-product repression by sterols when inserted into viral TK promoter
AU - Südhof, Thomas C.
AU - Russell, David W.
AU - Brown, Michael S.
AU - Goldstein, Joseph L.
N1 - Funding Information:
We thank Dr. Tim Osborne for many helpful suggestions. Amy Bolk and James Cali provided excellent technical assistance. This research was supported by research grants from the National Institutes of Health (HL 20948) and the Lucille P Markey Charitable Trust. D. W. R. is the recipient of a Research Career Development Award from the National Institutes of Health (HL 01287).
PY - 1987/3/27
Y1 - 1987/3/27
N2 - The LDL receptor, which mediates the cellular uptake of cholesterol, is subject to classic end-product repression when cholesterol accumulates in the cell. We here show that the sensitivity to end-product repression depends upon a 42 bp element in the 5′-flanking region of the human LDL receptor gene. This sequence, designated sterol regulatory element 42 (SRE 42), contains two 16 bp direct repeats that exhibit positive and negative transcriptional activities. Cells transfected with a fusion gene containing SRE 42 inserted into the promoter of the herpes simplex viral TK gene produced abundant mRNA when grown without sterols. When sterols were present, the mRNA was reduced by 57%-95%, depending on the number of copies of SRE in the fusion gene. These transfection data plus DNAase I footprinting experiments suggest a model of end-product repression in which the end product (sterols) opposes the action of a positive transcription factor that binds to a discrete promoter element.
AB - The LDL receptor, which mediates the cellular uptake of cholesterol, is subject to classic end-product repression when cholesterol accumulates in the cell. We here show that the sensitivity to end-product repression depends upon a 42 bp element in the 5′-flanking region of the human LDL receptor gene. This sequence, designated sterol regulatory element 42 (SRE 42), contains two 16 bp direct repeats that exhibit positive and negative transcriptional activities. Cells transfected with a fusion gene containing SRE 42 inserted into the promoter of the herpes simplex viral TK gene produced abundant mRNA when grown without sterols. When sterols were present, the mRNA was reduced by 57%-95%, depending on the number of copies of SRE in the fusion gene. These transfection data plus DNAase I footprinting experiments suggest a model of end-product repression in which the end product (sterols) opposes the action of a positive transcription factor that binds to a discrete promoter element.
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U2 - 10.1016/0092-8674(87)90713-6
DO - 10.1016/0092-8674(87)90713-6
M3 - Article
C2 - 3030558
AN - SCOPUS:0023666142
SN - 0092-8674
VL - 48
SP - 1061
EP - 1069
JO - Cell
JF - Cell
IS - 6
ER -