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Published on: September 16, 2019
Control of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Cancer
Anna Karpukhina1, Eugenia Tiukacheva2, Carla Dib3
1UMR 9018, CNRS, Université Paris Saclay, Institut Gustave Roussy, Villejuif F-94805, France; Koltzov Institute of Developmental Biology, Moscow 117334, Russia; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russia.
Abstract:
DUX4, a gene encoding a transcription factor involved in early embryogenesis, is located within the D4Z4 subtelomeric repeat on chromosome 4q35. In most healthy somatic tissues, DUX4 is heavily repressed by multiple genetic and epigenetic mechanisms, and its aberrant expression is linked to facioscapulohumeral muscular dystrophy (FSHD) where it has been extensively studied. Recently, DUX4 expression has been implicated in oncogenesis, although this is much less explored. In this review, we discuss multiple levels of control of DUX4 expression, including enhancer-promoter interactions, DNA methylation, histone modifications, noncoding RNAs, and telomere positioning effect. We also connect disparate data on intrachromosomal contacts involving DUX4 and emphasize the feedback loops in DUX4 regulation. Finally, we bridge data on DUX4 in FSHD and cancer and discuss prospective approaches for future FSHD therapies and the potential outcomes of DUX4 inhibition in cancer.
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