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Article Dans Une Revue Trends in Molecular Medicine Année : 2021

Control of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Cancer

Résumé

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 while 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, non-coding RNAs, and telomere positioning effect. We also connect disparate data on intra-chromosomal 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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Dates et versions

hal-03375995 , version 1 (16-10-2021)

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Anna Karpukhina, Eugenia Tiukacheva, Carla Dib, Yegor S Vassetzky, Svetlana Dokudovskaya. Control of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Cancer. Trends in Molecular Medicine, 2021, 27 (6), pp.588 - 601. ⟨10.1016/j.molmed.2021.03.008⟩. ⟨hal-03375995⟩
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