Cooperation by sterol regulatory element-binding protein and Sp1 in sterol regulation of low density lipoprotein receptor gene

H. B. Sanchez, L. Yieh, Timothy Osborne

Research output: Contribution to journalArticle

Abstract

Regulation of the low density lipoprotein (LDL) receptor promoter by cholesterol requires a well defined sterol regulatory site and an adjacent binding site for the universal transcription factor Sp1. These elements are located in repeats 2 and 3 of the wild type promoter, respectively. The experiments reported here demonstrate that Sp1 participates in sterol regulation of the LDL receptor in an orientation-specific fashion. We present data which suggest that sterol regulatory element-binding protein (SREBP) increases the binding of Sp1 to the adjacent repeat 3 sequence. We also demonstrate that SREBP and Sp1 synergistically activate expression from the LDL receptor promoter inside the cell by cotransfecting expression vectors encoding each protein into Drosophila tissue culture cells that are devoid of endogenous Sp1. In addition, other transcription factor sites were unable to substitute for Sp1 in sterol regulation when placed next to the SREBP- binding site. These studies together with recent data from others provide the basis of a working model for sterol regulation of the LDL receptor promoter. The presence of Sp1 sites in several other regulated promoters suggests that this universal transcription factor has been recruited to participate in many regulatory responses possibly by a similar mechanism.

Original languageEnglish (US)
Pages (from-to)1161-1169
Number of pages9
JournalJournal of Biological Chemistry
Volume270
Issue number3
DOIs
Publication statusPublished - Jan 1 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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