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Modeling the dynamics of bivalent histone modifications.

Ku WL, Girvan M, Yuan GC, Sorrentino F, Ott E - PLoS ONE (2013)

Bottom Line: It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear.Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns.We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Maryland, College Park, Maryland, United States of America ; Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains" in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.

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Space-time plots for the decay of  states.In these plots, all nucleosomes are initially () in the  state. Space-time plots of the average level of , , and  nucleosomes for , and  are shown in (A), (B), and (C), respectively. These plots are similar to Figure 4A and B. Here by level we mean the fraction of runs for which the nucleosomes is the indicated state. (D) Space-time plots for a single run with , , . , , , and  nucleosomes are plotted in red, yellow, green, and blue, respectively.
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pone-0077944-g006: Space-time plots for the decay of states.In these plots, all nucleosomes are initially () in the state. Space-time plots of the average level of , , and nucleosomes for , and are shown in (A), (B), and (C), respectively. These plots are similar to Figure 4A and B. Here by level we mean the fraction of runs for which the nucleosomes is the indicated state. (D) Space-time plots for a single run with , , . , , , and nucleosomes are plotted in red, yellow, green, and blue, respectively.

Mentions: In this section we use our model to simulate the decay of states. All parameters are the same as in section 4.1 except that and are taken to be non-zero. This is motivated by experimental findings that recruitment of demethylases is important for the decay of bivalent domains [22], [23], and occurs during cell differentiation. Also, we consider an initial condition in which all nucleosomes are in states. Results are shown in Figs. 6, 7, and 8 for different values of and keeping their ratio fixed at .


Modeling the dynamics of bivalent histone modifications.

Ku WL, Girvan M, Yuan GC, Sorrentino F, Ott E - PLoS ONE (2013)

Space-time plots for the decay of  states.In these plots, all nucleosomes are initially () in the  state. Space-time plots of the average level of , , and  nucleosomes for , and  are shown in (A), (B), and (C), respectively. These plots are similar to Figure 4A and B. Here by level we mean the fraction of runs for which the nucleosomes is the indicated state. (D) Space-time plots for a single run with , , . , , , and  nucleosomes are plotted in red, yellow, green, and blue, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815350&req=5

pone-0077944-g006: Space-time plots for the decay of states.In these plots, all nucleosomes are initially () in the state. Space-time plots of the average level of , , and nucleosomes for , and are shown in (A), (B), and (C), respectively. These plots are similar to Figure 4A and B. Here by level we mean the fraction of runs for which the nucleosomes is the indicated state. (D) Space-time plots for a single run with , , . , , , and nucleosomes are plotted in red, yellow, green, and blue, respectively.
Mentions: In this section we use our model to simulate the decay of states. All parameters are the same as in section 4.1 except that and are taken to be non-zero. This is motivated by experimental findings that recruitment of demethylases is important for the decay of bivalent domains [22], [23], and occurs during cell differentiation. Also, we consider an initial condition in which all nucleosomes are in states. Results are shown in Figs. 6, 7, and 8 for different values of and keeping their ratio fixed at .

Bottom Line: It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear.Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns.We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Maryland, College Park, Maryland, United States of America ; Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains" in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.

Show MeSH
Related in: MedlinePlus