Maybe because only a few people read this:
>>Published online before print September 26, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.2035056100
Applied Biological Sciences
Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity
Siyuan Tan *, Dmitry Guschin *, Albert Davalos , Ya-Li Lee *, Andrew W. Snowden *, Yann Jouvenot *, H. Steven Zhang *, Katherine Howes *, Andrew R. McNamara *, Albert Lai *, Chris Ullman *, Lindsey Reynolds *¶, Michael Moore *||, Mark Isalan *,**, Lutz-Peter Berg *, Bradley Campos *, Hong Qi *, S. Kaye Spratt *, Casey C. Case *, Carl O. Pabo *, Judith Campisi , and Philip D. Gregory *
*Sangamo BioSciences, Inc., Point Richmond Tech Center II, 501 Canal Boulevard, Richmond, CA 94804; and Lawrence Berkeley National Laboratory, Mailstop 84-171, 1 Cyclotron Road, Berkeley, CA 94720
Contributed by Carl O. Pabo, August 11, 2003
Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous CHK2 gene gives a >10-fold reduction in CHK2 mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics.<<
Cheers, Tuck |
