Double homeobox 4 (DUX4) (DUX4)

Double homeobox 4 (DUX4) is a transcription factor that is essential during the earliest stages of human development, where it initiates zygotic genome activation during the cleavage stage [1, 2]. In healthy adults, the DUX4 gene is epigenetically silenced in most somatic tissues, with expression restricted to the testes and thymus [3]. However, the aberrant reactivation and expression of DUX4 mRNA in skeletal muscle is the primary molecular cause of Facioscapulohumeral muscular dystrophy (FSHD) [4, 5]. This toxic gain-of-function leads to the activation of downstream genes that promote oxidative stress, DNA damage, and progressive muscle cell death [5, 6]. Consequently, therapeutic efforts are focused on degrading DUX4 mRNA using technologies such as siRNAs and antisense oligonucleotides, or inhibiting its transcription using small molecules like p38 MAPK inhibitors [7, 8]. The primary clinical challenge remains achieving high-affinity targeting and effective biodistribution to muscle tissue to halt disease progression [8].

Other names

Double homeobox 4 mRNADouble homeobox protein 4DUX4LDouble homeobox 4-likeDUX4 mRNA

Inhibition of DUX4 expression through RNA interference (siRNA) mediated degradation of mRNA, antisense oligonucleotide (ASO) mediated knockdown, or small molecule modulation of upstream signaling pathways such as p38 MAPK to prevent transcription.