Surveillance of Retroelement Expression and Nucleic-Acid Immunity by Histone Methyltransferase SETDB1

In human cancers, histone methyltransferase SETDB1 (SET domain, bifurcated 1) is frequently overexpressed but its significance in carcinogenesis remains elusive. A recent study shows that SETDB1 downregulation induces de-repression of retroelements and innate immunity in cancer cells. The possibility of SETDB1 functioning as a surveillant of retroelement expression is discussed in this study: the cytoplasmic presence of retroelement-derived nucleic acids (RdNAs) drives SETDB1 into the nucleus by the RNA-interference route, rendering the corresponding retroelement transcriptionally inert. These RdNAs could, therefore, be signals of genome instability sent out for SETDB1 present in the cytoplasm to maintain genome integrity.