Dynamics, stability and inheritance of somatic DNA methylation imprints

@article{citeulike:2258045, abstract = {Recent research highlights the role of CpG methylation in genomic imprinting, histone and chromatin modification, transcriptional regulation, and `gene silencing' in cancer development. An unresolved issue, however, is the role of stable inheritance of factors that manage epigenetic imprints in renewing or expanding cell populations in soma. Here we propose a mathematical model of CpG methylation that is consistent with the cooperative roles of de novo and maintenance methylation. This model describes (1) the evolution of methylation imprints toward stable, yet noisy equilibria, (2) bifurcations in methylation levels, thus the dual stability of both hypo- and hypermethylated genomic regions, and (3) sporadic transitions from hypo- to hypermethylated equilibria as a result of methylation noise in a finite system of CpG sites. Our model not only affords an explanation of the persistent coexistence of these two equilibria, but also of sporadic changes of site-specific methylation levels that may alter preset epigenetic imprints in a renewing cell population.}, author = {Sontag, Laura B. and Lorincz, Matthew C. and Georg}, citeulike-article-id = {2258045}, 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.jtbi.2006.05.012}, journal = {Journal of Theoretical Biology}, keywords = {inheritance, methylation}, month = {October}, number = {4}, pages = {890--899}, posted-at = {2008-01-19 20:31:13}, priority = {2}, title = {Dynamics, stability and inheritance of somatic DNA methylation imprints}, url = {http://dx.doi.org/10.1016/j.jtbi.2006.05.012}, volume = {242}, year = {2006} }

TY - JOUR ID - citeulike:2258045 L3 - citeulike-article-id:2258045 TI - Dynamics, stability and inheritance of somatic DNA methylation imprints JF - Journal of Theoretical Biology VL - 242 IS - 4 SP - 890 EP - 899 N2 - Recent research highlights the role of CpG methylation in genomic imprinting, histone and chromatin modification, transcriptional regulation, and `gene silencing' in cancer development. An unresolved issue, however, is the role of stable inheritance of factors that manage epigenetic imprints in renewing or expanding cell populations in soma. Here we propose a mathematical model of CpG methylation that is consistent with the cooperative roles of de novo and maintenance methylation. This model describes (1) the evolution of methylation imprints toward stable, yet noisy equilibria, (2) bifurcations in methylation levels, thus the dual stability of both hypo- and hypermethylated genomic regions, and (3) sporadic transitions from hypo- to hypermethylated equilibria as a result of methylation noise in a finite system of CpG sites. Our model not only affords an explanation of the persistent coexistence of these two equilibria, but also of sporadic changes of site-specific methylation levels that may alter preset epigenetic imprints in a renewing cell population. KW - inheritance KW - methylation 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 - Sontag, Laura AU - Lorincz, Matthew AU - Georg PY - 2006/10/21/ UR - http://dx.doi.org/10.1016/j.jtbi.2006.05.012 ER -