Awakening of the zygotic genome by pioneer transcription factors

After fertilization, the genome of the totipotent embryo is transcriptionally inactive and then initiates bursts of transcription termed zygotic genome activation (ZGA). Despite the fundamental importance of initiating an embryonic transcription program for the start of life, the essential regulators and molecular mechanisms triggering ZGA in most organisms are poorly understood. One mechanism centers on pioneer factors that function in cellular reprogramming and differentiation. Recent studies revealed that not only a single but multiple pioneer factors bind cooperatively to the genome to open chromatin, resulting in changes in epigenetic modifications and triggering ZGA. Here, we review recent insights into the functions of pioneer factors during ZGA and discuss the potential relevance to three-dimensional chromatin organization during embryonic development.