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Updated: Jun 20, 2026
11:34
Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Two adjacent nuclear factor-binding domains activate expression from the human PRNP promoter
Michael J Taheny1, Nerik Izkhakov, Alexander A Vostrov
1Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, Stony Brook, NY 11794-8101, USA. m_taheny@hotmail.com
BMC Research Notes
|September 11, 2009
Summary
Researchers identified two regulatory domains (prpA and prpB) in the human prion protein gene (PRNP) promoter. These domains bind factors that activate PRNP gene expression, offering potential therapeutic targets for prion diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
- Prion protein (PrPC) conversion to the pathological PrPSc isoform is central to TSEs.
- De novo PrP synthesis is necessary for disease progression, highlighting the PRNP gene promoter as a therapeutic target.
Purpose of the Study:
- To investigate the human prion protein gene (PRNP) promoter.
- To identify regulatory elements for potential therapeutic intervention in TSEs.
Main Methods:
- Transient transfection assays in HeLa cells.
- 5' deletion analysis of the PRNP promoter.
- DNase I footprinting to identify protected DNA regions.
- Mobility shift electrophoresis and methylation interference assays to analyze factor binding.
Main Results:
- Deletion analysis revealed a critical region for PRNP promoter activity between -90 and -232.
- DNase I footprinting identified two adjacent regulatory domains, prpA and prpB.
- Nuclear factor complexes bind to prpA and prpB, additively activating PRNP gene expression.
Conclusions:
- Two DNase I protected domains, prpA and prpB, were identified in the PRNP promoter.
- These domains are binding sites for unidentified regulatory factors.
- These factors independently activate PRNP gene expression, suggesting them as therapeutic targets.
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