Method and composition for identifying substances which activate transcription of the LDL receptor gene

US5378603A · kind A · utility

Assignee

• The Board of Regents of the University of Texas System · US

Inventors

• Michael S. Brown · Dallas, US
• Joseph L. Goldstein · Dallas, US
• David W. Russell · Dallas, US
• Thomas C. Sudhof · Dallas, US
• David W. Martin · San Francisco, US

Key dates

• Filing date: Mar 30, 1987
• Grant date: Jan 3, 1995
• Expiry date: Mar 30, 2007

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S436/817
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.