Bulliard Y Wiznerowicz M Barde I Trono D 2006 The KRAB transcriptional repressor domain, commonly found in zinc finger proteins, acts by inducing the formation of heterochromatin. We previously exploited this property to achieve drug-regulated transgenesis and knock down by combining doxycycline-controllable KRAB-containing fusion proteins and lentiviral vectors. Here, we asked whether KRAB-induced repression is widespread or limited to specific regions of the genome. For this, we transduced cells with a lentiviral vector expressing a target reporter and a KRAB-containing transcriptional repressor from a bicistronic mRNA. We found that approximately 1.4% of the resulting proviruses escaped repression. However, this phenotype could be reverted by expressing the KRAB-containing protein in trans. Accordingly, the irrepressible proviruses all contained, in the DNA sequence encoding the KRAB-containing effector or its upstream internal ribosomal entry site, mutations or deletions likely resulting from errors or recombination during reverse transcription. These results indicate that KRAB-induced transcriptional repression is robust and active over a variety of genomic contexts that include at least the wide range of sites targeted by lentiviral integration. application/pdf https://sonar.ch/global/documents/96746 eng info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M602843200 info:eu-repo/semantics/altIdentifier/pmid/16997916 info:eu-repo/semantics/openAccess The Journal of biological chemistry. - 2006 Binding Sites Cell Line Cell Separation DNA-Binding Proteins Doxycycline Gene Silencing Genetic Vectors Genome, Viral Humans Lentivirus Models, Genetic RNA, Messenger Repressor Proteins Transcription, Genetic Transgenes KRAB can repress lentivirus proviral transcription independently of integration site. http://purl.org/coar/resource_type/c_6501