2009
DOI: 10.1016/j.immuni.2008.12.009
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Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T Cells

Abstract: SUMMARY Multipotential naïve CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naïve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We fo… Show more

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Cited by 1,033 publications
(1,160 citation statements)
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References 61 publications
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“…63,64 One of the principle mechanisms that our model describes is derepression of cytokine loci through demethylation of CpG islets. Although there is ample evidence that epigenetic modification of histones contributes to the epigenetic regulation of cytokine loci, 6 we have chosen to describe only a single mechanism of epigenetic regulation in our models for reasons of simplicity. The models that we use are easily extendible to other types of epigenetic regulation, as illustrated by earlier studies that have modelled epigenetic modification of histones with similar mathematical formulations.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…63,64 One of the principle mechanisms that our model describes is derepression of cytokine loci through demethylation of CpG islets. Although there is ample evidence that epigenetic modification of histones contributes to the epigenetic regulation of cytokine loci, 6 we have chosen to describe only a single mechanism of epigenetic regulation in our models for reasons of simplicity. The models that we use are easily extendible to other types of epigenetic regulation, as illustrated by earlier studies that have modelled epigenetic modification of histones with similar mathematical formulations.…”
Section: Discussionmentioning
confidence: 99%
“…[4][5][6][7] The availability of quantitative data and the apparent complexity of cellular regulatory networks have led to a data-driven mathematical modelling approach that is usually referred to as computational or systems biology. Mathematical models have revealed nonlinearity in genetic networks that allow cells to switch between states.…”
mentioning
confidence: 99%
“…5a). However, their induction or co-expression in opposing subsets, especially with FOXP3, indicates that counter-regulation of their expression is incomplete 37,117 . Thus, these so-called master transcription factors behave less like lineage-definers and more like executors, expressed in response to environmental cues to carry out the induction of a defined set of gene effectors.…”
Section: Box 2 | Phenotypic Plasticity In Inflammatory and Regulatorymentioning
confidence: 99%
“…Many genes are thought to be maintained in a poised state in memory T‐cells, enabling rapid re‐expression of effector molecules following T‐cell reactivation by antigen‐presenting cells (APCs). However, epigenetic alterations to the genome are not fixed and memory cells can display plasticity 8, 9, 10, 11. The level of this plasticity is likely dependent on the extent of differentiation during the primary response and on the reactivation environment.…”
Section: Cytokine Production Is Key To Cd4 T‐cell Protective Immunitymentioning
confidence: 99%