TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells.
Moloney murine leukemia virus (M-MLV) replication is restricted in embryonic carcinoma (EC) and embryonic stem (ES) cells, likely to protect the germ line from insertional mutagenesis. Proviral DNAs are potently silenced at the level of transcription in these cells. This silencing is largely due to an unidentified trans-acting factor that is thought to bind to the primer binding site (PBS) of M-MLV and repress transcription from the viral promoter. We have partially purified a large PBS-mediated silencing complex and identified TRIM28 (Kap-1), a known transcriptional silencer, as an integral component of the complex. We show that RNAi-mediated knockdown of TRIM28 in EC and ES cells relieves the restriction and that TRIM28 is bound to the PBS in vivo when restriction takes place. The identification of TRIM28 as a retroviral silencer adds to the growing body of evidence that many TRIM family proteins are involved in retroviral restriction.
Wolf
Daniel
D
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Goff
Stephen P
SP
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28; D014779:Virus Replication / Q000502:physiology
D004279:DNA, Viral; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28