Small interfering RNA-induced transcriptional gene silencing in human cells.
Science (New York, N.Y.) 2004 Aug 27; 305(5688):1289-92
Morris K KV, Chan S SW, Jacobsen S SE, Looney D DJ
Department of Medicine 0678, Stein Clinical Research Building, Room 302, University of California-San Diego, La Jolla, CA 92093-0678, USA. kmorris@coh.org
Small interfering RNA (siRNA) and microRNA silence genes at the transcriptional, posttranscriptional, and/or translational level. Using human tissue culture cells, we show that promoter-directed siRNA inhibits transcription of an integrated, proviral, elongation factor 1alpha (EF1A) promoter-green fluorescent protein reporter gene and of endogenous EF1A. Silencing was associated with DNA methylation of the targeted sequence, and it required either active transport of siRNA into the nucleus or permeabilization of the nuclear envelope by lentiviral transduction. These results demonstrate that siRNA-directed transcriptional silencing is conserved in mammals, providing a means to inhibit mammalian gene function.