Sterol Regulatory Elements

US5256545A · 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

Key dates

• Filing date: Oct 20, 1989
• Grant date: Oct 26, 1993
• Expiry date: Oct 20, 2009

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N15/85
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Disclosed are discrete functionally translocatable DNA segments, termed Sterol Regulatory Elements (SREs), 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 repeat 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 discrete 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.