title: Nucleation and spreading of a heterochromatic domain in fission yeast.
abstract: 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 ∼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.
authors.affiliation: Department of Biology, University of Copenhagen, BioCenter, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Michaela J
authors.initials: MJ
authors.lastname: Obersriebnig
authors.affiliation: Department of Biology, University of Copenhagen, BioCenter, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Emil M H
authors.initials: EM
authors.lastname: Pallesen
authors.affiliation: Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
authors.affiliation: Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
authors.forename: Ala
authors.initials: A
authors.lastname: Trusina
authors.affiliation: Department of Biology, University of Copenhagen, BioCenter, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Thon
mesh_terms: D005456:Fluorescent Dyes / Q000378:metabolism; D020868:Gene Silencing; D017930:Genes, Reporter; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D059010:Single-Cell Analysis; D013269:Stochastic Processes
chemical_list: D005456:Fluorescent Dyes; D006570:Heterochromatin; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D008239:Lysine