The impact of cellular metabolism on chromatin dynamics and epigenetics

Reid, Michael A.; Dai, Ziwei; Locasale, Jason W.

doi:10.1038/ncb3629

Cited by 416 publications

(387 citation statements)

References 160 publications

Supporting

Mentioning

362

Contrasting

Unclassified

Order By: Relevance

“…Deficient GLS activity may alter differentiation through production of cofactors, including α-KG and 2-hydroxyglutarate (2-HG), for epigenetic marks and changes in chromatin status (Reid et al, 2017; Xu et al, 2017). Intracellular levels of α-KG were reduced in CB839-treated Th1 but not Th17 cells, while 2-HG increased in both Th1 and Th17 (Figures S5A and S5B).…”

Section: Resultsmentioning

confidence: 99%

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism

Johnson

Wolf

Madden

et al. 2018

Cell

Self Cite

518

413

View full text Add to dashboard Cite

SUMMARY Activated T cells differentiate into functional subsets with distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in T cell activation and specification. Though GLS deficiency diminished initial T cell activation and proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet to promote differentiation and effector function of CD4 Th1 and CD8 CTL cells. This was associated with altered chromatin accessibility and gene expression, including decreased PIK3IP1 in Th1 cells that sensitized to IL-2-mediated mTORC1 signaling. In vivo, GLS null T cells failed to drive Th17-inflammatory diseases, and Th1 cells had initially elevated function but exhausted over time. Transient GLS inhibition, however, led to increased Th1 and CTL T cell numbers. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism

Johnson

Wolf

Madden

et al. 2018

Cell

Self Cite

518

413

View full text Add to dashboard Cite

show abstract

“…30,73 This supports the concept that that memory T-cell differentiation could be linked with epigenetic modifications at specific loci and that these cells are epigenetically poised to respond to secondary stimulation. Metabolic substrates can directly and indirectly alter a cell's epigenetic profile, 34,74 thus it is probable that the epigenetic profile of memory T cells is at least in part influenced or maintained by metabolic conditions within the cells. An example of this could be the production of the metabolite 2-hydroxygluterate (S-2-HG), which is increased in activated T cells.…”

Section: Metabolic Signaling and Epigenetics In Memory T Cellsmentioning

confidence: 99%

The metabolic spectrum of memory T cells

O’Sullivan

2019

Immunol Cell Biol

View full text Add to dashboard Cite

The development and persistence of memory T cells are integral to effective host defenses. Cell metabolism has a central role in the maintenance of these populations and engagement of specific metabolic pathways can influence T‐cell fate. Nuances in memory T‐cell metabolism are both context dependent, and exist, on a spectrum that complements and supports the activity of specific memory T‐cell subsets. This review explores how metabolic pathways and substrate choice can influence the phenotype and function of memory T cells.

show abstract

“…It has become evident that the cellular chromatin state is dynamically linked to metabolic and homeostatic perturbations, not only by providing a flexible platform for metabolic gene expression programs but also by acting as an intrinsic rheostat of carbon flux and cellular pH (van der Knaap & Verrijzer, 2016). As has been reviewed extensively elsewhere, the activity of histone‐ and nucleic acid‐modifying enzymes relies on (and is influenced by) the availability of specific substrates, intermediates, and products from diverse metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty acid β‐oxidation, methionine cycle, and glutamine metabolism (Etchegaray & Mostoslavsky, 2016; Li, Egervari, Wang, Berger, & Lu, 2018; Nieborak & Schneider, 2018; Reid, Dai, & Locasale, 2017; Schvartzman, Thompson, & Finley, 2018; Sharma & Rando, 2017; van der Knaap & Verrijzer, 2016). Consequently, shifts in substrate selection and energy provision in the exercising muscle may have multiple acute implications on chromatin dynamics and epigenetic modifications.…”

Section: Skeletal Muscle Exercise and Flexible Epigenomementioning

confidence: 99%

Transcriptional memory in skeletal muscle. Don't forget (to) exercise

Beiter

Nieß

Moser

2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training‐induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.

show abstract

The impact of cellular metabolism on chromatin dynamics and epigenetics

Cited by 416 publications

References 160 publications

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism

The metabolic spectrum of memory T cells

Transcriptional memory in skeletal muscle. Don't forget (to) exercise

Contact Info

Product

Resources

About