Related Experiment Video
Updated: Feb 16, 2026
11:12
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
8.4K
Enhancer transcription reveals subtype-specific gene expression programs controlling breast cancer pathogenesis
Hector L Franco1, Anusha Nagari1, Venkat S Malladi1
1Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genome Research
|December 24, 2017
Summary
Active enhancers drive gene expression in breast cancer. This study identifies key transcription factors (TFs) like FOSL1 that regulate cancer cell growth and patient prognosis, particularly in triple-negative breast cancer (TNBC).
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Noncoding transcription from enhancers is crucial for gene regulation.
- Understanding enhancer activity in breast cancer subtypes is vital for identifying therapeutic targets.
Purpose of the Study:
- To investigate the link between enhancer activity and biological outcomes in diverse breast cancer subtypes.
- To develop and validate a computational pipeline for identifying subtype-specific enhancers and their associated transcription factors (TFs).
Main Methods:
- Profiling transcriptomes (GRO-seq, RNA-seq) and epigenomes (ChIP-seq) of 13 human breast cell lines.
- Developing a computational pipeline integrating enhancer transcription, TF expression, motif analysis, and epigenetic marks (H3K4me1, H3K27ac).
- Utilizing the Total Functional Score of Enhancer Elements (TFSEE) for TF identification.
Main Results:
- The TFSEE pipeline successfully identified key breast cancer subtype-specific TFs, including Forkhead TFs, FOSL1, and PLAG1.
- FOSL1 was highly enriched at enhancers in triple-negative breast cancer (TNBC) cells, regulating their proliferation and viability.
- FOSL1 expression correlated with poor prognosis in TNBC patients.
Conclusions:
- The developed enhancer identification pipeline is robust and effective.
- Transcribed enhancers play a critical role in directing gene regulatory networks that drive breast cancer pathogenesis.
- Identifying specific TFs like FOSL1 at enhancers offers potential therapeutic strategies for breast cancer subtypes.
Related Concept Videos
01:33Cancer-Critical Genes I: Proto-oncogenes
11.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.5K
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
01:37Epigenetic Regulation
3.9K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.9K
01:46Epigenetic Regulation
33.9K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.9K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.9K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K
01:58Cell Specific Gene Expression
16.7K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.7K