Gene activation by triplex-forming oligonucleotide coupled to the activating domain of protein VP16

S Kuznetsova; S Ait-Si-Ali; I Nagibneva; F Troalen; J P Le Villain; A Harel-Bellan; F Svinarchuk

doi:10.1093/nar/27.20.3995

Gene activation by triplex-forming oligonucleotide coupled to the activating domain of protein VP16

Nucleic Acids Res. 1999 Oct 15;27(20):3995-4000. doi: 10.1093/nar/27.20.3995.

Authors

S Kuznetsova¹, S Ait-Si-Ali, I Nagibneva, F Troalen, J P Le Villain, A Harel-Bellan, F Svinarchuk

Affiliation

¹ Laboratory of Nucleic Acid Chemistry, Lomonosov Moscow State University, Leninskie gory, 119899, Moscow, Russia.

Abstract

Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit transcription or DNA replication but can be used for more diverse purposes. Here we have designed a chimera peptide-TFO able to activate transcription from a target gene. The designed hybrid molecule contains a triplex-forming sequence, linked through a phosphoroamidate bond to several minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). We show here that this TFO-peptide chimera (TFO-P) can specifically recognise its DNA target at physiological salt and pH conditions. Bound to the double-stranded target DNA in a promoter region, the TFO-P is able to activate gene expression. Our results suggest that this type of molecule may prove useful in the design of new tools for artificial modulation of gene expression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Cell Line
Gene Expression Regulation*
Herpes Simplex Virus Protein Vmw65 / metabolism*
Molecular Sequence Data
Nucleic Acid Conformation
Oligonucleotides / metabolism*
Transcriptional Activation

Substances

Herpes Simplex Virus Protein Vmw65
Oligonucleotides