Related Experiment Video
Updated: Aug 21, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter
1Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abstract:
Human NRH:quinone oxidoreductase 2 (NQO2) gene-containing 29-bp deletion/insertion polymorphic promoters were found to be associated with susceptibility to Parkinson's disease. Here, we demonstrate that the NQO2 gene is differentially expressed by the polymorphic promoters in human fibroblasts and Hep-G2 cells transfected with NQO2 gene reporter constructs. Promoter containing the 29-bp insertion polymorphism demonstrated significantly lower NQO2 gene expression. Deletion mutagenesis and DNase I footprinting analysis of the promoter without the 29-bp insertion identified three protected regions (region A, B, and C). Band- and supershift and transfection assays showed binding of transcription factor Sp1 to regions A and B, which regulated expression of the NQO2 gene. Similar studies of the NQO2 gene promoter with the 29-bp insertion polymorphism showed that regions A and C were identical and contributed similarly as in the promoter without the 29-bp insertion to NQO2 gene expression. However, region B was found to be inserted with 29-bp DNA element and bound to both Sp1 and Sp3. Binding of Sp3 led to repression of NQO2 gene transcription by the promoter containing the 29-bp insertion polymorphism. These studies also suggest that alterations in NQO2 activity might be an important factor in susceptibility to Parkinson's disease.
Related Concept Videos
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Co-activators and Co-repressors
RNA Polymerase II Accessory Proteins
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Chromatin Structure Regulates pre-mRNA Processing
The chromatin structure, especially...
Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon has three reading...
