Scientists identify the two molecules that activate life itself. Chromosomes contributed by the egg and sperm form a unique genome within hours of fertilization. Initially, however, this new genome is inactive and must be “awakened” for the DNA transcription process to facilitate embryonic development.
Antonio Giraldez is the Fergus F. Wallace Professor of Genetics and chair of the Department of Genetics at Yale University.
“This is the beginning of life from a molecular standpoint,” said Professor Giraldez. “What hasn’t been clear is how and what kick-starts the transcriptional activity of the embryonic genome, so that the embryo starts taking control of its own development with its own genetic blueprint.”
The researchers identified two specific factors that are needed to activate DNA in a new genome. They examined the first step of DNA-based gene expression, or transcription, in the nucleus of a zebrafish embryo using a combination of microscopy and RNA sequencing analysis.
The experts developed tools that would allow them to visualize the first activated gene in the zebrafish genome, miR-430, so that its activity could be traced in living embryos.
“Now we can visually look inside the nucleus and analyze how the first gene within the silent genome is awakened,” said study lead author and doctoral student Shun Hang Chan.
The team found that the presence of two proteins produced by the mother, P300 and Brd4, are required for the activation of the zebrafish genome. When the researchers disrupted the activity of these two proteins using small molecule inhibitors, the activation of the embryonic genome was prevented. As a result, the development of the embryo was blocked.Scientists identify the two molecules that activate life itself
The researchers discovered, however, that they could prematurely trigger the activation of the embryonic genome by artificially introducing P300 and Brd4, even after the production of the maternal proteins was inhibited.
“These molecular factors act as a sort of molecular timer, which sets the timing of genome’s awakening,” said Professor Giraldez. “Finding these key factors involved in genome activation serve as the critical first step towards our understanding of how life begins.”
The study is published in the journal Developmental Cell.
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