Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11518
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Funding
- Lundbeck Foundation
- Danish National Research Foundation (C-MOL Center)
- Novo Nordisk Foundation
- Danish Council for Independent Research
- University of Copenhagen Center of Excellence MolPhysX
- Lundbeck Foundation [R9-2007-867] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0017448] Funding Source: researchfish
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Outstanding questions in the chromatin field bear on how large heterochromatin domains are formed in space and time. Positive feedback, where histone-modifying enzymes are attracted to chromosomal regions displaying the modification they catalyse, is believed to drive the formation of these domains; however, few quantitative studies are available to assess this hypothesis. Here we quantified the de novo establishment of a naturally occurring similar to 20-kb heterochromatin domain in fission yeast through single-cell analyses, measuring the kinetics of heterochromatin nucleation in a region targeted by RNAi and its subsequent expansion. We found that nucleation of heterochromatin is stochastic and can take from one to ten cell generations. Further silencing of the full region takes another one to ten generations. Quantitative modelling of the observed kinetics emphasizes the importance of local feedback, where a nucleosome-bound enzyme modifies adjacent nucleosomes, combined with a feedback where recruited enzymes can act at a distance.
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