Only part of the D4Z4 region is necessary for epigenetic repression of DUX4

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the abnormal and delayed expression of a transcriptionTransfert de l’information génétique d’un gène à partir d’une molécule d’ADN en ARN messager (transcrit). factor called DUX4, which has a deleterious effect on adult muscle fibers. American and Dutch researchers have precisely characterized the D4Z4 region where the DUX4 gene is located:

• several fragments of the region of interest (D4Z4) were then studied in terms of their epigenetic status, using a reporter gene.
• A specific sequence in the region, composed of 126 nucleotides, was identified as responsible for hypermethylation under the effect of epigenetic factors.

This fundamental research paves the way for possible therapeutic advances, particularly with the use of more targeted compounds that act on chromatin structure, such as histone deacetylase (HDAC) inhibitors.

A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing. Paatela EM, St Amant FG, Hamm DC et al. Hum Mol Genet. 2025 Jul