A11 - Silencing mechanisms of endogenous retroviruses
Endogenous retroviruses (ERVs) compose a significant portion of mammalian genomes. Aberrant expression of ERVs is connected to human diseases. A prominent silencing pathway for many ERV families involves establishment of H3K9me3 and DNA methylation. During the last years, we and others have identified proteins involved in heterochromatin formation on ERVs. It turned out that there are three major pathways involved: (1) H3K9me3 establishment by Setdb1, (2) DNA methylation by Dnmt1/Uhrf1 and (3) H3.3 deposition by Atrx/Daxx. In this proposal we want to deepen our knowledge on these protein interaction networks with focus on the interplay between the proteins involved and the regulation of their activities to induce ERV silencing.