In a newly fertilized egg, the genome doesn’t mobilize all at once. Just a few genes are activated at first, then a few more, day by day. The exact order in which our genes “light up” has been understood but dimly, but a new study has glimpsed new details. Out of roughly 23,000 human genes, 32 are switched on two days after fertilization, and by day three, there are 129 activated genes.

These results appeared September 3 in the journal Nature Communications, in an article entitled, “Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development.” The article pointed out that seven of the genes found and characterized in the study had not been discovered previously.

These details promise to illuminate the regulation of early human development. In addition, they may lead to the identification of new factors for use in cell reprogramming and the maintenance of pluripotency, advancing our understanding of induced pluripotent stem cells.

“[By] using single-cell RNA sequencing of 348 oocytes, zygotes, and single blastomeres from 2- and 3-day-old embryos, we provide a detailed analysis of the human preimplantation transcriptome,” wrote the authors of the Nature Communications article. “By quantifying transcript far 5′ ends (TFEs), we include in our analysis transcripts that derive from alternative promoters.”

These methods allowed the study’s authors, scientists based at Karolinska Institutet, to examine how some genes interact with stretches of so-called junk DNA, such as Alu elements, a class of repetitive DNA. Alu elements appear play a role in controlling transcription through their influence on RNA processing. In the current study, Alu elements were found to overlap with DNA sequences around upregulated TFEs that were significantly enriched with gene regulatory motifs.

“Our results provide novel insights into the regulation of early embryonic development in human,” said one of the paper’s senior authors, Outi Hovatta, M.D., Ph.D., professor at Karolinska Institutet's Department of Clinical Science, Intervention and Technology. “We identified novel factors that might be used in reprogramming cells into so-called pluripotent stem cells for possible treatment of a range of diseases, and potentially also in the treatment of infertility.”

The authors noted that some of the transcripts identified in the study originate from previously unannotated genes. These include the novel PRD-like homeobox genes ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, and LEUTX.

These genes, together with the other genes identified in the study, “are the 'ignition key' that is needed to turn on human embryonic development,” asserted the study’s principal investigator, Juha Kere, M.D., Ph.D., professor at the Department of Bio-sciences and Nutrition at Karolinska Institutet. “It is like dropping a stone into water and then watching the waves spread across the surface.”








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