Theoretical analysis of epigenetic cell memory by nucleosome modification
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Theoretical analysis of epigenetic cell memory by nucleosome modification. / Dodd, Ian B; Micheelsen, Mille A; Sneppen, Kim; Thon, Genevieve.
I: Cell, Bind 129, Nr. 4, 2007, s. 813-22.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Theoretical analysis of epigenetic cell memory by nucleosome modification
AU - Dodd, Ian B
AU - Micheelsen, Mille A
AU - Sneppen, Kim
AU - Thon, Genevieve
N1 - KEYWORDS: Cell Nucleus; Chromosomal Instability; DNA Replication; Epigenesis, Genetic; Feedback, Biochemical; Models, Biological; Nucleosomes; Schizosaccharomyces; Stochastic Processes
PY - 2007
Y1 - 2007
N2 - Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Such epigenetic control is often associated with alternative covalent modifications of histones. The stability and heritability of the states are thought to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes. We developed a simplified stochastic model for dynamic nucleosome modification based on the silent mating-type region of the yeast Schizosaccharomyces pombe. We show that the mechanism can give strong bistability that is resistant both to high noise due to random gain or loss of nucleosome modifications and to random partitioning upon DNA replication. However, robust bistability required: (1) cooperativity, the activity of more than one modified nucleosome, in the modification reactions and (2) that nucleosomes occasionally stimulate modification beyond their neighbor nucleosomes, arguing against a simple continuous spreading of nucleosome modification.
AB - Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Such epigenetic control is often associated with alternative covalent modifications of histones. The stability and heritability of the states are thought to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes. We developed a simplified stochastic model for dynamic nucleosome modification based on the silent mating-type region of the yeast Schizosaccharomyces pombe. We show that the mechanism can give strong bistability that is resistant both to high noise due to random gain or loss of nucleosome modifications and to random partitioning upon DNA replication. However, robust bistability required: (1) cooperativity, the activity of more than one modified nucleosome, in the modification reactions and (2) that nucleosomes occasionally stimulate modification beyond their neighbor nucleosomes, arguing against a simple continuous spreading of nucleosome modification.
U2 - 10.1016/j.cell.2007.02.053
DO - 10.1016/j.cell.2007.02.053
M3 - Journal article
C2 - 17512413
VL - 129
SP - 813
EP - 822
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -
ID: 9179119