Theoretical Analysis of Epigenetic Cell Memory by Nucleosome Modification

@article{citeulike:1320002, abstract = {Summary 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.}, author = {Dodd, Ian B. and Micheelsen, Mille A. and Sneppen, Kim and Thon, Genevieve }, citeulike-article-id = {1320002}, comment = {Fourth, theoretical modeling will provide a way to fathom our mechanistic and quantitative understanding of epigenetic mechanisms. For example, two recent studies could show that co-operativity among the proteins that write epigenetic information is required for stably maintaining the state of an epigenetic switch in the presence of highly dynamic fluctuations at the molecular level (Dodd et al., 2007; Sontag et al., 2006). Modeling studies can thus help explain how the high-level phenomena that we observe for epigenetic regulation emerge from the dynamic interplay of various epigenetic mechanisms. - Bock et al 2007}, doi = {10.1016/j.cell.2007.02.053}, journal = {Cell}, keywords = {epigenetics, histone-modifications, mechanisms, modeling}, month = {May}, number = {4}, pages = {813--822}, posted-at = {2008-01-19 20:33:02}, priority = {2}, title = {Theoretical Analysis of Epigenetic Cell Memory by Nucleosome Modification}, url = {http://dx.doi.org/10.1016/j.cell.2007.02.053}, volume = {129}, year = {2007} }

TY - JOUR ID - citeulike:1320002 L3 - citeulike-article-id:1320002 TI - Theoretical Analysis of Epigenetic Cell Memory by Nucleosome Modification JF - Cell VL - 129 IS - 4 SP - 813 EP - 822 N2 - Summary 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. KW - epigenetics KW - histone-modifications KW - mechanisms KW - modeling N1 - Fourth, theoretical modeling will provide a way to fathom our mechanistic and quantitative understanding of epigenetic mechanisms. For example, two recent studies could show that co-operativity among the proteins that write epigenetic information is required for stably maintaining the state of an epigenetic switch in the presence of highly dynamic fluctuations at the molecular level (Dodd et al., 2007; Sontag et al., 2006). Modeling studies can thus help explain how the high-level phenomena that we observe for epigenetic regulation emerge from the dynamic interplay of various epigenetic mechanisms. - Bock et al 2007 AU - Dodd, Ian AU - Micheelsen, Mille AU - Sneppen, Kim AU - Thon, Genevieve PY - 2007/05/18/ UR - http://dx.doi.org/10.1016/j.cell.2007.02.053 ER -