Related Experiment Video
Updated: Dec 15, 2025
09:58
An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides
Published on: November 29, 2016
16.5K
The Pathognomonic FOXL2 C134W Mutation Alters DNA-Binding Specificity.
Annaïck Carles1, Genny Trigo-Gonzalez2,3, Qi Cao1
1Department of Microbiology and Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
Cancer Research
|July 10, 2020
Summary
The FOXL2 C134W mutation drives adult-type granulosa cell tumors (AGCT) by altering DNA binding and gene expression. This finding reveals new therapeutic strategies for AGCT.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- The FOXL2 C134W mutation is a key diagnostic marker for adult-type granulosa cell tumors (AGCT).
- The precise molecular mechanisms by which this mutation contributes to AGCT pathogenesis are not fully understood.
Purpose of the Study:
- To elucidate the molecular consequences of the FOXL2 C134W mutation.
- To identify novel molecular targets and therapeutic strategies for AGCT.
Main Methods:
- Engineered inducible isogenic cell lines expressing wild-type (WT) or mutant (C134W) V5-FOXL2.
- Performed chromatin immunoprecipitation sequencing (ChIP-seq) to analyze DNA-binding alterations.
- Conducted transcriptome profiling to assess changes in gene expression.
Main Results:
- FOXL2 C134W exhibits altered DNA-binding specificity, associating with both shared and unique genomic elements compared to WT FOXL2.
- Identified novel direct targets of FOXL2 C134W, including SLC35F2.
- Demonstrated that increased SLC35F2 expression enhances sensitivity to the therapeutic agent YM155.
Conclusions:
- The FOXL2 C134W mutation drives AGCT by reprogramming the transcriptional landscape through altered DNA-binding.
- Targeting unique FOXL2 C134W-driven regulatory pathways, such as SLC35F2, offers a promising therapeutic avenue for AGCT.
Related Concept Videos
01:33Pleiotropy
42.9K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
42.9K
01:49Conserved Binding Sites
4.9K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.9K
02:53Conservative Site-specific Recombination and Phase Variation
6.5K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.5K
02:32Position-effect Variegation
6.9K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.9K
02:23Master Transcription Regulators
7.6K
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...
7.6K
02:02Cis-regulatory Sequences
11.4K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.4K