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

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...

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Bibliographic Details
Published in:Molecular bioSystems 2009-01, Vol.5 (2), p.143-150
Main Authors: Galbete, José Luis, Buceta, Montserrat, Mermod, Nicolas
Format: Article
Language:English
Subjects:
Animals
CHO Cells
Cricetinae
Cricetulus
Epigenesis, Genetic
Flow Cytometry
Gene Expression Regulation
Gene Silencing
Genetic Engineering
Humans
Matrix Attachment Regions - genetics
Models, Theoretical
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transgenes
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Summary: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.
ISSN:1742-206X
1742-2051
DOI:10.1039/b813657b