title: MAR elements regulate the probability of epigenetic switching between active and inactive gene expression.
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.
authors.affiliation: Institute of Biotechnology, University of Lausanne, CH-1015, Lausanne, Switzerland.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Galbete
authors.forename: Montserrat
authors.initials: M
authors.lastname: Buceta
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mermod
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005818:Genetic Engineering; D006801:Humans; D045170:Matrix Attachment Regions / Q000235:genetics*; D008962:Models, Theoretical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019076:Transgenes