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Updated: Jul 4, 2026

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
Identification of a novel repressor element in the cyclo-oxygenase-2 promoter and its nuclear binding protein
Xiaomin Yang1, Ling Lin, Xiongfei Zhang
1Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
Abstract:
Cyclo-oxygenase-2 (COX-2) has important functions in many diseases. Although its transcriptional regulation has been investigated in considerable detail, some important elements remain unknown. The aim of the present study was to demonstrate the existence of a novel repressor element in the mouse COX-2 promoter and characterize some of its binding proteins. In order to identify the repressor element, the activity of the mouse COX-2 promoter was investigated in the pancreatic beta-cell line RINm5F using a series of deletion and mutant constructs. The ability of nuclear proteins to bind to this repressor element was then determined by an electrophoretic mobility shift assay and the proteins binding to this repressor element were purified and identified by mass spectrometry. One of the nuclear proteins identified was overexpressed to examine its inhibitory effect on COX-2 promoter activity. We found a novel repressor element located from nucleotides -655 to -632 of the mouse COX-2 promoter region. Some proteins from RINm5F cell nuclear extracts bound to this element, one of which was identified as non-POU-domain-containing, octamer-binding protein (NonO). Overexpression of NonO significantly inhibited wild-type COX-2 promoter activity, but had no effect when the repressor element was mutated. In conclusion, we have demonstrated that a regulatory 'spot' is present in the COX-2 promoter. This provides additional data on COX-2 gene regulation and may provide an insight into the clinical treatment of diseases where COX-2 is highly expressed.
Insights
Researchers discovered a new repressor element in the mouse cyclo-oxygenase-2 (COX-2) promoter. This element, bound by the protein NonO, inhibits COX-2 gene activity, offering insights into disease regulation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Cyclo-oxygenase-2 (COX-2) plays a significant role in various diseases.
- Transcriptional regulation of COX-2 is extensively studied, yet some regulatory elements remain unidentified.
Purpose of the Study:
- To identify and characterize a novel repressor element within the mouse COX-2 promoter.
- To identify proteins that bind to this novel repressor element.
Main Methods:
- Utilized deletion and mutant constructs of the mouse COX-2 promoter in RINm5F cells.
- Employed electrophoretic mobility shift assays to detect protein binding.
- Purified and identified binding proteins using mass spectrometry.
- Assessed the functional impact of NonO overexpression on COX-2 promoter activity.
Main Results:
- Identified a novel repressor element in the mouse COX-2 promoter region (-655 to -632).
- Determined that the protein NonO binds to this repressor element.
- Demonstrated that NonO overexpression significantly inhibits wild-type COX-2 promoter activity, but not when the repressor element is mutated.
Conclusions:
- A novel regulatory repressor element exists in the COX-2 promoter.
- The protein NonO acts as a repressor for COX-2 gene activity.
- Findings contribute to understanding COX-2 gene regulation and may inform therapeutic strategies for diseases involving COX-2 overexpression.
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