Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells
Gene transfer in eukaryotic cells and organisms suffers from epigenetic effects that result in low or unstable transgene expression and high clonal variability. Use of epigenetic regulators such as matrix attachment regions (MARs) is a promising approach to alleviate such unwanted effects. Dissection of a known MAR allowed the identification of sequence motifs that mediate elevated transgene expression. Bioinformatics analysis implied that these motifs adopt a curved DNA structure that positions nucleosomes and binds specific transcription factors. From these observations, we computed putative MARs from the human genome. Cloning of several predicted MARs indicated that they are much more potent than the previously known element, boosting the expression of recombinant proteins from cultured cells as well as mediating high and sustained expression in mice. Thus we computationally identified potent epigenetic regulators, opening new strategies toward high and stable transgene expression for research, therapeutic production or gene-based therapies.
 Institute of Biotechnology, University of Lausanne, and Center for Biotechnology of the University of Lausanne and Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland.  Present addresses: Selexis SA, 18 Ch. des Aulx, Geneva, Switzerland (P.A.G., D.C., A.R.), MRC Functional Genetics Unit, University of Oxford, Oxford OX1 3TG, UK (D.-Q.N.).
Record created on 2007-12-17, modified on 2016-08-08