Targeting chromatin features unique to DUX4-expressing cells

Investigator: Fran Sverdrup PhD

Category: Research - Basic

A major obstacle to understanding how the normally silent DUX4 gene is turned on in FSHD is the fact that only a small percentage of FSHD muscle cells express DUX4 at any one time. We have employed a method to isolate a pure population of FSHD muscle cells with DUX4 turned on in every cell! This has enabled high resolution analysis of DNA regions that are potentially responsible for turning on DUX4. Using this system, we have identified novel potential regulatory regions with features unique to the small fraction of cells in which DUX4 is actively turned on. We will systematically target these regions with CRISPR activator and repressor technology to reveal DUX4-regulatory characteristics of these regions. Identification of key regulatory regions will enable more efficient and stabile epigenetic repression of DUX4 using therapeutic CRISPR-dCas9 repressor technology.