Issue 2, 2009
From the journal:

Molecular BioSystems

MAR elements regulate the probability of epigenetic switching between active and inactive gene expression†

José Luis Galbete,a   Montserrat Buceta‡a  and  Nicolas Mermod§*ab  

* Corresponding authors

a Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland

b Molecular Biotechnology Laboratory, Station 6, Lausanne, Switzerland
E-mail: Nicolas.Mermod@unil.ch
Fax: +41 21 693 76 10
Tel: +41 21 693 61 51

Abstract

Gene expression often cycles between active and inactive states in eukaryotes, yielding variable or noisy gene expression in the short-term, while slow epigenetic changes may lead to silencing or variegated expression. Understanding how cells control these effects will be of paramount importance to construct biological systems with predictable behaviours. Here we find that a human matrix attachment region (MAR) genetic element controls the stability and heritability of gene expression in cell populations. Mathematical modeling indicated that the MAR controls the probability of long-term transitions between active and inactive expression, thus reducing silencing effects and increasing the reactivation of silent genes. Single-cell short-terms assays revealed persistent expression and reduced expression noise in MAR-driven genes, while stochastic burst of expression occurred without this genetic element. The MAR thus confers a more deterministic behavior to an otherwise stochastic process, providing a means towards more reliable expression of engineered genetic systems.

Graphical abstract: MAR elements regulate the probability of epigenetic switching between active and inactive gene expression

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Article information

DOI
https://doi.org/10.1039/B813657B
Article type
Method
Submitted
06 Aug 2008
Accepted
03 Nov 2008
First published
05 Dec 2008

Mol. BioSyst., 2009,5, 143-150

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MAR elements regulate the probability of epigenetic switching between active and inactive gene expression

J. Luis Galbete, M. Buceta and N. Mermod, Mol. BioSyst., 2009, 5, 143 DOI: 10.1039/B813657B

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