Light activated recombination

J Am Chem Soc. 2005 Sep 28;127(38):13088-9. doi: 10.1021/ja0531226.

Abstract

Many genes elicit their actions through their expression in precise spatial patterns in tissues. Photoregulated expression systems offer a means to remotely pattern gene expression in tissues. Using currently available photopatterning methods, gene expression is only transient. Herein is described a general method to permanently alter a cell's genome under the control of light. The photocaged estrogen receptor (ER) antagonists, nitroveratryl-hydroxytamoxifen (Nv-HTam) and nitroveratryl-hydroxytamoxifen aziridine (Nv-HTaz), mediate exposure-dependent recombination in cells expressing the Cre-ER, a fusion of the site-specific recombinase Cre and ER. Both Nv-HTam and Nv-HTaz only activate recombination by Cre-ER after exposure to light. When released only intracellularly, the covalent-modifying Taz can mediate significant amounts of recombination in an exposure-dependent manner. Nv-HTaz and Cre-ER represent perhaps the first compound that can be used to photopattern gene expression through recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Light*
  • Molecular Structure
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / metabolism
  • Recombination, Genetic*
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / chemistry
  • Tamoxifen / pharmacology
  • beta-Galactosidase / drug effects
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Receptors, Estrogen
  • Tamoxifen
  • afimoxifene
  • beta-Galactosidase