Gene regulation: Silencing factor for endogenous retroviruses identified

Over time, many endogenous retrovirus (ERV) sequences have integrated into the human genome, and now play important roles in normal gene regulation. However, high levels of expression of ERV transcripts can lead to disorders such as autoimmune diseases and cancers.

Based on a genome-wide screen, a team led by Gunnar Schotta at LMU‘s Biomedical Center has identified the protein Morc3 as a new factor involved in the silencing of ERVs. Whether a given gene is expressed is largely determined by how its DNA sequence is packaged by histone proteins in the complex known as chromatin. The new study shows that Morc3 triggers a modification of packaging by enabling the localized incorporation of the histone variant H3.3 into chromatin, which is mediated by the protein Daxx. This modification results in the formation of a condensed chromatin structure that inhibits the activation of ERV genes.

Sophia Groh, Anna Viktoria Milton, Lisa Katherina Marinelli, Cara V. Sickinger, Angela Russo, Heike Bollig, Gustavo Pereira de Almeida, Andreas Schmidt, Ignasi Forné, Axel Imhof and Gunnar Schotta: Morc3 silences endogenous retroviruses by enabling Daxx mediated histone H3.3 incorporation. Nature Communications 2021