Related Experiment Video
Updated: Aug 3, 2026
11:27
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes
Michal Krawczyk1, Beverly M Emerson2
1Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
Elife
|May 21, 2014
Summary
Researchers discovered a new way cyclooxygenase-2 (COX-2) is controlled at the gene level. A long non-coding RNA (lncRNA) called PACER helps regulate COX-2, offering a potential new target for cancer and inflammation therapies.
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- Deregulated cyclooxygenase-2 (COX-2) expression is implicated in human cancer development, progression, and patient outcomes.
- Understanding the precise transcriptional control mechanisms of COX-2 is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate a novel mechanism of transcriptional control for COX-2 expression.
- To identify the role of long non-coding RNA (lncRNA) in regulating COX-2 gene expression.
- To investigate the potential of the identified lncRNA as a therapeutic target.
Main Methods:
- Utilized primary human mammary epithelial cells and monocyte/macrophage cell lines.
- Investigated the function of CTCF (a chromatin boundary factor) in COX-2 promoter regulation.
- Analyzed the interaction of a novel lncRNA (PACER) with NF-κB subunits (p50 and p65) and p300 histone acetyltransferase.
Main Results:
- CTCF establishes an open chromatin domain and induces PACER lncRNA expression upstream of COX-2.
- PACER associates with the repressive p50 subunit of NF-κB, occluding it from the COX-2 promoter.
- This occlusion facilitates the recruitment of p300, leading to increased histone acetylation and RNA Polymerase II complex assembly, thereby inducing COX-2 expression.
Conclusions:
- A novel mechanism of gene regulation involving lncRNA-mediated repressor occlusion has been identified.
- The COX-2-lncRNA, PACER, plays a critical role in transcriptional control of COX-2.
- PACER represents a potential new therapeutic target for modulating COX-2 in inflammation and cancer.
More Related Videos
09:52A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Related Concept Videos
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...