DUX4, a Zygotic Genome Activator, Is Involved in Oncogenesis and Genetic Diseases

摘要

After fertilization, the genome is transcriptionally quiescent to allow zygote reprogramming that relies on the RNA and proteins accumulated in the oocyte and ensures the transition from the differentiated germ cells to a totipotent state. Reprogramming is followed by zygotic genome activation (ZGA).DUX4gene encoding for a double homeobox transcription factor is one of the key ZGA drivers in humans. Its expression, essential for embryo development, is subject to precise temporal regulation and is normally observed only at early cleavage stages.DUX4is efficiently silenced in most somatic tissues via numerous epigenetic mechanisms, while its aberrant expression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD).DUX4expression following chromosomal rearrangements is also observed in a subset of leukemias and sarcomas; it leads to anti-cancer immune activity suppression.