Identification of epigenetic regulatory elements to mediate transgene expression in mammalian cells and in vivo

Prague, Czech Republic (June 20, 2008)

Institute of Biotechnology, AS CR, v.v.i.

takes the pleasure to invite you to attend the lecture on regulation of transgene expression

Identification of epigenetic regulatory elements mediating transgene expressionin mammalian cells and in vivo

presented by

Nicolas MermodUniversity of Lausanne

on Friday 20 June 2 pm

groundfloor Lecture Hall of Institute of Molecular Genetics AS CR, v.v.i., Praha Krc

basic reading:

Girod PA, Nguyen DQ, Calabrese D, Puttini S, Grandjean M,Martinet D, Regamey A,Saugy D, Beckmann JS, Bucher P, Mermod N. (2007). Genome-wide predictionof matrix attachment regions that increase gene expression in mammaliancells. Nat Methods. 2007 Sep;4(9):747-53.

Gene transfer in eukaryotic cells and organisms suffers from epigeneticeffectsthat result in low or unstable transgene expression and high clonalvariability.Use of epigenetic regulators such as matrix attachment regions (MARs) isapromising approach to alleviate such unwanted effects. Dissection of a known MARallowed the identification of sequence motifs that mediate elevatedtransgeneexpression. Bioinformatics analysis implied that these motifs adopt a curved DNAstructure that positions nucleosomes and binds specific transcriptionfactors.From these observations, we computed putative MARs from the humangenome. Cloningof several predicted MARs indicated that they are much more potent thanthepreviously known element, boosting the expression of recombinant proteinsfromcultured cells as well as mediating high and sustained expression inmice. Thuswe computationally identified potent epigenetic regulators, opening newstrategies toward high and stable transgene expression for research,therapeuticproduction or gene-based therapies.

How to get to the seminar: ze stanice "Poliklinika Budejovicka" - metro "C" - autobusem c. 193 na konecnou "Ustavy Akademie ved " - 15 min///////////////////////////////Kontakt:Peter Sebo, PhD.GSM: (+420) 774 798 121office phone: (+420) 241 063 613 (secretary and voice mail)fax: (+420) 241 062 152mail: sebo(at)biomed.cas.czhttp://www.ibt.cas.cz/

More: http://www.ibt.cas.cz/