Epigenetic regulation of a non-coding RNA implicated in FSHD pathogenesis
Facioscapulohumeral muscular dystrophy (FSHD) is a common and debilitating myopathy very frequently associated with decreased D4Z4 repetitive element copy number at chromosome 4q35. The exact molecular mechanism driving FSHD is unknown, however, epigenetic dysregulation is suspected to be a major contributing factor.
In a recent report published in Cell, Cabianca et al. show that a reduction in D4Z4 copy number at 4q35 leads to loss of Polycomb group protein-mediated epigenetic gene repression, followed by expression of a non-coding RNA (ncRNA) termed DBE-T, or D4Z4 binding element-transcript. The authors found that DBE-T coordinates the de-repression of 4q35 gene expression by recruiting the Trithorax group protein Ash1L to the FSHD locus, which causes modification of the surrounding chromatin structure.
The findings put forth by Cabianca et al. shed light on the ability of repetitive elements and ncRNAs to influence epigenetic regulation of gene expression and human disease. Finally, this study suggests that DBE-T may be a valuable therapeutic target to treat FSHD patients.
View Full Paper: http://www.cell.com/retrieve/pii/S0092867412004631