SETDB1 and H3K9me3 play various roles in multiple tissues. SETDB1 is expressed in almost all cell types in mammals, and various functions have been established for SETDB1 in different tissues. In the embryonic stem cells, SETDB1 represses the differentiation-associated genes to maintain the pluripotency. And repression of chimeric transcripts may also contribute to the process49. On the other hand, SETDB1- dependent repression of endogenous retrovirus is crucial to proper development of various pluripotent stem cells, including primordial germ cells, T cells and gut stem cells. In most of these cases, aberrant activation of endogenous retrovirus resulted from Setdb1 deficiency leads to cell death19,50,51. Interestingly, cell death is not detectable in the Setdb1 knockout cells in this current study. Therefore, the roles of SETDB1 are variable, which is dependent on different master regulators and microenvironment.
