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The first days of an embryo and viral DNA resurgence

2- (top) and 8-cells (bottom) embryos stages. Activated retrotransposons are in pink and green.

Jan. 29, 2013

The development of an embryo is very specific. The team of Maria-Elena Torres-Padilla at the IGBMC has brought to light an unusual DNA state, specific of the beginning of development, and which is accompanied with a targeted activation of viral genetic sequences which are otherwise usually silenced: the endogenous retrotransposons. These results are published on 27th January in Nature Structural & Molecular Biology.


The embryonic chromatin

Chromatin is the form under which the DNA is packed in the cell nucleus. It is either in an open and active state, or under a compacted and inactive form. This condensed form is called “heterochromatin” while the open one is known as “euchromatin”. The latter allows the DNA to be transcribed and translated into proteins. In their latest study, researchers from Maria-Elena Torres-Padilla team at the IGBMC describe an “atypic” state of chromatin at the beginning of embryonic development, which is not typical for euchromatin, nor for heterochromatin, but is rather an an open and accessible configuration.

 

Activation of endogenous retrotransposons

Our genome contains about 50% of inactive repetitive sequences. Researchers suspected that some of them, the retrotransposons, were derepressed in the early embryo, probably because of a more accessible chromatin at this stage. Actually, a lot of RNA is found in the oocyte after fertilisation, but it was not known whether retrotransposon RNA in the embryo was solely from maternal inheritance. This hypothesis has just been adressed by Maria-Elena’s group who demonstrated for the first time in vivo that the epigenetic reprogramming that follows after the fertilisation is accompanied by the activation of retrotransposons, which are otherwise usually repressed in somatic cells.

 

New small RNAs

They have also revealed that retrotransposon activation is initiated by a new class of very small RNAs of only 17 nucleotides, i.e. smaller than well-known microRNA or siRNA which are 21 nucleotides. These small RNAs would be involved in a stimulatory auto-enhancing loop.

 

This new study is providing new elements for a better understanding of the regulation of gene expression regulation in the very first steps of the development of the mammalian embryo. The activation of retrotransposons can lead to genetic retrotransposition or recombination, compromising genome integrity, thereby resulting in cancer or potentially in defective implantation of the embryo during pregnancy. A better understanding of the mechanisms underlying the derepression of retrotransposons could help to explain the development of some tumors and defaults linked to infertility.

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