DUX-Family Proteins Trigger Zygote Genome Activation; Discovery Is Landmark in Developmental Biology

The formation of a human embryo begins with the fertilization of the oocyte by the sperm cell. This yields the zygote, the primordial cell that carries one copy each of the maternal and the paternal genomes. However, this genetic information starts being expressed only after the zygote divides a couple of times. But what triggers this process, called "zygotic genome activation," was unknown until now. EPFL (Ecole Polytechnique Fédérale de Lausanne) scientists in Switrzerland have just found that members of the DUX family of proteins are responsible for igniting the gene expression program of the nascent embryo. Published online on May 1, 2017 in Nature Genetics, this discovery is a milestone for developmental biology. The article is titled “DUX-Family Transcription Factors Regulate Zygotic Genome Activation In Placental Mammals.” Lead author Dr. Alberto de Iaco, a postdoc in the lab of Dr. Didier Trono at EPFL, drew upon a seemingly irrelevant study of patients suffering from a form of muscular dystrophy where mutations lead to the production in muscle cells of a protein called DUX4, which is normally detected only at the earliest stage of human embryonic development. Dr. De Iaco also found that when DUX4 is forcibly produced in muscle cells, it turns on a whole set of genes that are expressed during zygotic genome activation. This was what first suggested that DUX4 could be the key regulator of this seminal event. To confirm this, the researchers analyzed publicly available data to determine what components of the human genome are expressed during the first few days of embryonic development. They found that DUX4 is one of the very first genes expressed at this stage, releasing a high concentration of its protein product just before zygotic genome activation.
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