Regulation Of Retroviral Silencing In Different Cell Types

The replication of Moloney Murine Leukemia Virus (MoMLV or MLV) is restricted in mouse embryonic stem (ES) and embryonic carcinoma (EC) cells, but not in differentiated cells. The restriction is mediated by the primer binding site (PBS) of proviral DNA of MLV. A restriction complex can bind to the PBS of MLV and block the transcription of viral genes. Two major components of the PBS-mediated silencing complex were identified in our lab, ZFP809 and Trim28. ZFP809 contains two conserved domains, a zinc finger domain responsible for DNA binding and a KRAB box recruiting Trim28, and hence other transcription repressors, such as HP1γ and ESET. A protein called L1td1 was identified during the purification of PBS-mediated restriction complex. L1td1 is a stem cell specific protein but little is known about the function of L1td1. In differentiated cells, the replication of MLV is not restricted. Overexpression of ZFP809 in differentiated cells is sufficient to re-establish the PBS mediated restriction. However, data from various expression libraries shows that the mRNA levels of ZFP809 in stem cells and differentiated cells are approximately the same, which indicating that there is some pos