Research provides new insights into molecular basis of X-chromosome inactivation

Research provides new insights into molecular basis of X-chromosome inactivation

Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg and Institut Curie in Paris have shown that the protein SPEN plays a crucial role in the process of X-chromosome inactivation, whereby female mammalian embryos silence gene expression on one of their two X chromosomes. In their landmark research published in Nature on 5 February, the scientists reveal how SPEN targets and silences active genes on the X chromosome, providing important new insights into the molecular basis of X-inactivation. SPEN protein (green) in living cells. Image credit: François Dossin In mammals, males and females differ genetically in their sex chromosomes – XX in females and XY in males. This leads to a potential imbalance, as more than a thousand genes on the X chromosome would be expressed in a double dose in females compared to males. To avoid this imbalance, which has been shown to lead to early embryonic lethality, female embryos shut down the expression of genes on one of their two X chromosomes. Scientists did not fully understand how genes actually become silenced on the X chromosome, although a molecule called Xist is known to initiate the process. Xist is a long non-coding RNA – a type of molecule created using the cell’s DNA as a template, but one which doesn’t carry instructions for making a protein. Xist coats the chromosome from which it is expressed and induces silencing. “The exact molecular mechanisms by which Xist mediates gene silencing have been a mystery for decades,” says EMBL/Curie PhD student François Dossin. In the new study, he and his colleagues in the Heard Group in Heidelberg, previously at Institut Curie in Paris, have identified how SPEN – a key player in X-chromosome inactivation – functions to induce gene silencing in mouse embryos and embryonic stem cells . This study provides some of the first detailed molecular insights into X-inactivation since its discovery in 1961 by Mary Lyon. Related Stories



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