Gene regulation: DNA modification important for silencing of endogenous retroviruses

Endogenous retroviruses (ERVs) have established themselves in the human genome in the course of evolution and play a major role in normal gene regulation. Excessive ERV activity, however, can lead to diseases such as autoimmunity and cancer. And so cells have developed mechanisms for recognizing and silencing endogenous retroviruses. The silencing is accomplished by packaging the corresponding DNA sections into a less accessible structure. This process is facilitated by modifications to the histone proteins that package the DNA (H3K9me3) and a modification to the DNA itself (DNA methylation). It has not been clear before now, however, which of these modifications are really important for ERV silencing.

A team led by Gunnar Schotta from LMU’s Biomedical Center Munich has found that in certain cell types, DNA methylation is decisive and the presence of H3K9me3 is not sufficient to silence ERVs. This discovery furnishes an important basis, for example, for the investigation of aberrantly activated ERVs in the context of diseases such as cancer and autoimmunity.

Zeyang Wang, Rui Fan, Angela Russo, Filippo M. Cernilogar, Alexander Nuber, Silvia Schirge, Irina Shcherbakova, Iva Dzhilyanova, Enes Ugur, Tobias Anton, Lisa Richter, Heinrich Leonhardt, Heiko Lickert, Gunnar Schotta: Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm. Nature Communications 2022