Karpukhina Anna, Tiukacheva Eugenia, Dib Carla, Vassetzky Yegor S
UMR 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.
UMR 9018, CNRS, Université Paris Saclay, Institut Gustave Roussy, Villejuif F-94805, France.
Trends Mol Med. 2021 Jun;27(6):588-601. doi: 10.1016/j.molmed.2021.03.008. Epub 2021 Apr 13.
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.
DUX4是一种编码参与早期胚胎发育的转录因子的基因，位于4号染色体4q35的D4Z4亚端粒重复序列内。在大多数健康的体细胞组织中，DUX4受到多种遗传和表观遗传机制的强烈抑制，其异常表达与面肩肱型肌营养不良症（FSHD）有关，对此已进行了广泛研究。最近，DUX4的表达与肿瘤发生有关，尽管这方面的研究较少。在这篇综述中，我们讨论了DUX4表达的多个调控层面，包括增强子-启动子相互作用、DNA甲基化、组蛋白修饰、非编码RNA和端粒定位效应。我们还将涉及DUX4的染色体内部接触的不同数据联系起来，并强调DUX4调控中的反馈回路。最后，我们将FSHD和癌症中关于DUX4的数据联系起来，讨论未来FSHD治疗的前瞻性方法以及抑制DUX4在癌症中的潜在结果。
