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

• Published in: Russian journal of developmental biology Vol. 51; no. 3; pp. 176 - 182
• Main Authors: Karpukhina, Anna, Vassetzky, Yegor
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.05.2020; Springer Nature B.V; MAIK Nauka/Interperiodica
• Subjects: Animal Anatomy; Biomedical and Life Sciences; carcinogenesis; Cell differentiation; Chromosome rearrangements; Developmental Biology; embryogenesis; epigenetics; Fertilization; genes; Genomes; Germ cells; Histology; Homeobox; Life Sciences; Morphology; Muscular dystrophy; oocytes; Reviews; Ribonucleic acid; RNA; Skeletal muscle; transcription (genetics); transcription factors; Tumorigenesis; zygote; zygotic genome activation (ZGA); muscular dystrophy; DUX4; oncogenesis
• ISSN: 1062-3604; 1608-3326
• DOI: 10.1134/S1062360420030078

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). DUX4 gene 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. DUX4 is efficiently silenced in most somatic tissues via numerous epigenetic mechanisms, while its aberrant expression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). DUX4 expression following chromosomal rearrangements is also observed in a subset of leukemias and sarcomas; it leads to anti-cancer immune activity suppression.