title: Light activated recombination.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Kristian H
authors.initials: KH
authors.lastname: Link
authors.forename: Youheng
authors.initials: Y
authors.lastname: Shi
authors.forename: John T
authors.initials: JT
authors.lastname: Koh
mesh_terms: D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008027:Light; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011995:Recombination, Genetic; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001616:beta-Galactosidase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D001616:beta-Galactosidase