Revelation from New Human Genome Awakening

Some genes are active from the get-go challenges the textbook view that genes don't become active in human embryos until they are made up of four-to-eight cells, two or three days after fertilization.

The newly discovered activity begins at the one-cell stage far sooner than previously thought � promising to change the way we think about our developmental origins. The finding is published in Cell Stem Cell.

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‘Activation of genes gives essential instructions to all cells including the embryo cells.’

Using a method called RNA-sequencing, researchers applied precision analysis to individual human eggs and one-cell embryos to make a detailed inventory of tell-tale products of gene activity, called RNA transcripts.

It revealed that hundreds of genes awaken in human one-cell embryos. Because the gene activity starts small, previous techniques had not been sensitive enough to detect it. But state-of-the-art RNA-sequencing used in this study was able to reveal even small changes.

"This is the first good look at the beginning of a biological process that we all go through � the transit through the one-cell embryo stage," said Professor Perry, from the Department of Biology and Biochemistry at Bath.

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Researchers found that many genes activated in one-cell embryos remain switched on until the four-to-eight cell stage, at which point they are switched off.

At the moment of human fertilization, the collection of sperm and egg genomes is inactive. The sperm and egg rely on transcripts produced when they were being formed for instructions that regulate their characteristics.

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Understanding the process of genome awakening is important for genetic diseases, inheritance, and infertility. The scientists found some activated genes that might be expected to play roles in early embryos, but the roles of others were unknown and could point to embryonic events that we don't yet understand.

Remarkably, candidates that might trigger gene activation include factors usually associated with cancer, such as some well-known oncogenes.

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This led the researchers to speculate that the natural, healthy role of factors that are known to misbehave in cancer, is to awaken genes in one-cell embryos.

If this proves to be correct, research findings could illuminate events that initiate cancer, providing new diagnostic and preventive opportunities.

The findings also have clinical implications for the inheritance of acquired traits, such as obesity: parents who gain weight seem to pass the trait to their kids. It is not known how such acquired traits are transmitted, but altering gene activation after fertilization is a possible mechanism.

The team also looked at unhealthy one-cell embryos that do not go on to develop and found that many of their genes fail to activate.

Abnormal embryos have been used to evaluate methods of human heritable genome editing, but the new findings suggest they may be inappropriate as a reliable test system.

Source-Medindia