Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells.

Details

Serval ID
serval:BIB_FBEEC01204C1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells.
Journal
Nature Methods
Author(s)
Girod P.A., Nguyen D.Q., Calabrese D., Puttini S., Grandjean M., Martinet D., Regamey A., Saugy D., Beckmann J.S., Bucher P., Mermod N.
ISSN
1548-7091[print], 1548-7091[linking]
Publication state
Published
Issued date
09/2007
Volume
4
Number
9
Pages
747-753
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Animals, CHO Cells, Chickens, Cloning, Molecular, Computational Biology/methods, Cricetinae, Cricetulus, Gene Expression, Genome, Human, Humans, Matrix Attachment Regions/genetics, Mice, Molecular Sequence Data, Recombinant Proteins/biosynthesis, Transfection, Transgenes
Pubmed
Web of science
Create date
25/01/2008 17:17
Last modification date
20/08/2019 17:27
Usage data