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Spatial epigenetic control of mono- and bistable gene expression
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 961796
Author(s) Kelemen, János Z.; Ratna, Prasuna; Scherrer, Simone; Becskei, Attila
Author(s) at UniBasel Becskei, Attila
Year 2010
Title Spatial epigenetic control of mono- and bistable gene expression
Journal PLoS Biology
Volume 8
Number 3
Pages / Article-Number e1000332
Abstract Bistability in signaling networks is frequently employed to promote stochastic switch-like transitions between cellular differentiation states. Differentiation can also be triggered by antagonism of activators and repressors mediated by epigenetic processes that constitute regulatory circuits anchored to the chromosome. Their regulatory logic has remained unclear. A reaction-diffusion model reveals that the same reaction mechanism can support both graded monostable and switch-like bistable gene expression, depending on whether recruited repressor proteins generate a single silencing gradient or two interacting gradients that flank a gene. Our experiments confirm that chromosomal recruitment of activator and repressor proteins permits a plastic form of control; the stability of gene expression is determined by the spatial distribution of silencing nucleation sites along the chromosome. The unveiled regulatory principles will help to understand the mechanisms of variegated gene expression, to design synthetic genetic networks that combine transcriptional regulatory motifs with chromatin-based epigenetic effects, and to control cellular differentiation.
Publisher Public Library of Science
ISSN/ISBN 1544-9173 ; 1545-7885
edoc-URL http://edoc.unibas.ch/46405/
Full Text on edoc No
Digital Object Identifier DOI 10.1371/journal.pbio.1000332
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/20305717
ISI-Number WOS:000278125400011
Document type (ISI) Journal Article
 
   

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