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Circles Of Life: Linking Metabolic And Epigenetic Cycles To Immunity

C. Lio, Stanley Ching‐Cheng Huang
Published 2020 · Biology, Medicine

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Metabolites are the essential substrates for epigenetic modification enzymes to write or erase the epigenetic blueprint in cells. Hence, the availability of nutrients and activity of metabolic pathways strongly influence the enzymatic function. Recent studies have shed light on the choreography between metabolome and epigenome in the control of immune cell differentiation and function, with a major focus on histone modifications. Yet, despite its importance in gene regulation, DNA methylation and its relationship with metabolism is relatively unclear. In this review, we will describe how the metabolic flux can influence epigenetic networks in innate and adaptive immune cells, with a focus on the DNA methylation cycle and the metabolites S‐adenosylmethionine and α‐ketoglutarate. Future directions will be discussed for this rapidly emerging field.
This paper references
10.1016/0014-4827(78)90070-8
Arrest of cell growth in the G1 phase of the cell cycle by serine deprivation.
R. Allen (1978)
10.1074/jbc.272.25.16040
Differential Regulation of Methionine Adenosyltransferase in Superantigen and Mitogen Stimulated Human T Lymphocytes*
H. Legros (1997)
10.1111/j.1749-6632.1999.tb07818.x
The α‐Ketoglutarate Dehydrogenase Complex
K. Rex Sheu (1999)
10.1016/S1074-7613(01)00227-8
A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.
P. Lee (2001)
10.1038/ni1004
Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells
K. Makar (2003)
10.1158/0008-5472.CAN-05-1961
Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells.
A. R. Karpf (2005)
10.1098/rstb.2005.1764
Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress
L. Tretter (2005)
10.1073/pnas.0605944103
Testing gene function early in the B cell lineage in mb1-cre mice
E. Hobeika (2006)
10.4049/jimmunol.176.8.4562
DNA Methylation by DNA Methyltransferase 1 Is Critical for Effector CD8 T Cell Expansion1
Craig P. Chappell (2006)
10.1016/j.cell.2007.02.006
Epigenetics: A Landscape Takes Shape
A. Goldberg (2007)
10.1385/MN:31:1-3:043
The α-ketoglutarate-dehydrogenase complex
G. Gibson (2007)
10.4049/jimmunol.0803320
Cutting Edge: TCR Stimulation Is Sufficient for Induction of Foxp3 Expression in the Absence of DNA Methyltransferase 11
S. Josefowicz (2009)
10.1016/j.bbabio.2009.01.019
Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells.
E. Griffiths (2009)
10.1126/science.1170116
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
M. Tahiliani (2009)
10.4049/jimmunol.0802960
Identification of DNA Methyltransferase 3a as a T Cell Receptor-Induced Regulator of Th1 and Th2 Differentiation1
C. Gamper (2009)
10.1016/J.FREERADBIOMED.2010.10.256
α-Ketoglutarate Dehydrogenase: A Mitochondrial Redox Sensor
Aaron L. McLain (2010)
10.1016/j.sbi.2010.08.006
Structural studies on human 2-oxoglutarate dependent oxygenases.
M. McDonough (2010)
10.1016/j.bbadis.2009.08.010
Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases.
G. Gibson (2010)
10.1038/nrg2719
Establishing, maintaining and modifying DNA methylation patterns in plants and animals
Julie A. Law (2010)
10.1073/pnas.1112317108
Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice
M. Ko (2011)
10.1016/j.immuni.2011.06.015
Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8(+) T cells.
Ben Youngblood (2011)
10.1016/j.stem.2011.07.010
Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.
M. Dawlaty (2011)
10.3109/10715762.2010.534163
α-Ketoglutarate dehydrogenase: A mitochondrial redox sensor
Aaron L. McLain (2011)
10.1038/nature10443
The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
Tianpeng Gu (2011)
10.1182/blood-2011-06-357996
DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation.
R. Shaknovich (2011)
Ten-ElevenTranslocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice
M Ko (2011)
10.1074/jbc.M111.312785
De Novo DNA Methylation Is Required to Restrict T Helper Lineage Plasticity*
Rajan M Thomas (2012)
10.1038/nri3155
Selection of regulatory T cells in the thymus
C. Hsieh (2012)
10.1038/nrc3343
The role of mutations in epigenetic regulators in myeloid malignancies
A. Shih (2012)
10.1182/blood-2012-08-451765
Foxp3+ T-regulatory cells require DNA methyltransferase 1 expression to prevent development of lethal autoimmunity.
Liqing Wang (2013)
10.4049/jimmunol.1301395
Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function
Christopher D. Scharer (2013)
10.1038/nature11743
Serine starvation induces stress and p53 dependent metabolic remodeling in cancer cells
O. Maddocks (2012)
10.1016/j.mcn.2012.07.005
An update on the role of mitochondrial α-ketoglutarate dehydrogenase in oxidative stress
A. Starkov (2013)
10.1016/j.cell.2013.03.004
Influence of Metabolism on Epigenetics and Disease
W. Kaelin (2013)
10.1016/j.molimm.2012.12.014
TET1 is a negative transcriptional regulator of IL-1β in the THP-1 cell line.
A. Neves-Costa (2013)
10.1016/j.stem.2014.06.018
Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells.
G. Challen (2014)
10.1073/pnas.1412327111
Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation
Ageliki Tsagaratou (2014)
10.1038/nri3777
Epigenetic control of myeloid cell differentiation, identity and function
D. Álvarez-Errico (2014)
10.1210/me.2013-1293
Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b.
Xiaosong Yang (2014)
10.1002/eji.201445035
De novo DNA Methyltransferases Dnmt3a and Dnmt3b regulate the onset of Igκ light chain rearrangement during early B‐cell development
A. Manoharan (2015)
10.1038/nature15252
Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6
Q. Zhang (2015)
10.1038/nature14192
Function and information content of DNA methylation
D. Schübeler (2015)
10.1016/j.immuni.2015.03.005
The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells.
K. Ichiyama (2015)
10.1016/j.celrep.2015.09.051
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
G. Caron (2015)
10.1073/pnas.1510510112
Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis
Jinsuk Kang (2015)
10.7554/eLife.18290
Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility
C. Lio (2016)
10.1016/j.celrep.2016.05.091
5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells.
C. Nestor (2016)
10.1038/emm.2016.35
S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress
Sun-young Yoon (2016)
10.1038/ng.3488
DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia
C. Oakes (2016)
S-2-hydroxyglutarate regulates CD 8 + T-lymphocyte fate
P. Tyrakis (2016)
10.1084/jem.20151438
Control of Foxp3 stability through modulation of TET activity
X. Yue (2016)
10.1016/j.cmet.2016.06.007
Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.
N. Ron-Harel (2016)
10.1073/pnas.1524490113
De novo DNA methylation by DNA methyltransferase 3a controls early effector CD8+ T-cell fate decisions following activation
Brian H. Ladle (2016)
10.1038/ni.3464
Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity
Xia Li (2016)
10.1038/nature20165
The immunometabolite S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate
P. Tyrakis (2016)
10.1073/pnas.1604365113
Tissue-specific DNA demethylation is required for proper B-cell differentiation and function
S. Orlanski (2016)
10.1016/j.molcel.2016.05.029
Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes.
J. Etchegaray (2016)
10.1172/jci.insight.87748
Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity.
Xianfeng Wang (2016)
10.1038/ni.3519
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation
B. Barwick (2016)
5Hydroxymethylcytosine remodeling precedes lineage specification during differentiation of human CD4
CE Nestor (2016)
10.1038/ni.3630
TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells
Ageliki Tsagaratou (2017)
10.1016/j.cmet.2016.08.009
One-Carbon Metabolism in Health and Disease.
Gregory S. Ducker (2017)
10.1146/annurev-biochem-061516-044732
Isocitrate Dehydrogenase Mutation and (R)-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development.
L. Dang (2017)
10.1038/nature25144
EFFECTOR CD8 T CELLS DEDIFFERENTIATE INTO LONG-LIVED MEMORY CELLS
Ben Youngblood (2017)
10.1126/science.aag1381
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
J. Fuster (2017)
10.1016/j.immuni.2017.07.015
CCCTC‐Binding Factor Translates Interleukin 2‐ and &agr;‐Ketoglutarate‐Sensitive Metabolic Changes in T Cells into Context‐Dependent Gene Programs
Danielle A. Chisolm (2017)
10.1016/j.exphem.2017.08.001
Tet2 restrains inflammatory gene expression in macrophages.
A. Cull (2017)
10.1016/j.immuni.2017.07.020
The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor‐Infiltrating Myeloid Cells to Promote Melanoma Progression
Wen Pan (2017)
10.1016/j.cell.2017.06.007
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Hazem E. Ghoneim (2017)
10.1016/j.cmet.2016.12.011
Serine Is an Essential Metabolite for Effector T Cell Expansion.
E. H. Ma (2017)
10.1016/j.cell.2017.04.004
Metabolic Instruction of Immunity
M. D. Buck (2017)
10.1038/ni.3796
α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming
Pu-Ste Liu (2017)
CCCTCBinding factor translates interleukin 2- and a-ketoglutarate-sensitive metabolic changes in T cells into context-dependent gene programs. Immunity 2017; 47:251–267.e7
DK Crossman (2017)
10.1158/2159-8290.CD-18-0657
TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis.
Pilar M. Dominguez (2018)
10.1073/pnas.1804149115
Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice
N. Ron-Harel (2018)
10.1016/j.stem.2018.01.011
Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies.
R. Bowman (2018)
10.1038/s41467-018-04234-4
B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation
B. Barwick (2018)
10.1038/s41586-018-0178-z
Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells
J. Fraietta (2018)
10.4049/jimmunol.1700559
The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation
S. Carty (2018)
10.1038/s41586-018-0846-z
Mitochondrial complex III is essential for regulatory T cell suppressive function
S. Weinberg (2018)
10.1016/j.tem.2018.02.002
Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions
D. Bargiela (2018)
10.1038/nri.2017.146
Epigenetic control of CD8+ T cell differentiation
A. Henning (2018)
10.1038/s41588-018-0290-x
Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution
Efrat Shema (2018)
10.1182/blood.2019791475
Dysregulation of the TET family of epigenetic regulators in hematopoietic malignancies.
C. Lio (2019)
10.1126/sciimmunol.aau7523
TET enzymes augment activation-induced deaminase (AID) expression via 5-hydroxymethylcytosine modifications at the Aicda superenhancer
C. Lio (2019)
10.1038/s41571-019-0203-7
Navigating metabolic pathways to enhance antitumour immunity and immunotherapy
Xiaoyun Li (2019)
10.7554/eLife.44210
Antigen receptor control of methionine metabolism in T cells
L. Sinclair (2019)
10.1016/j.molcel.2019.06.039
One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages.
Weiwei Yu (2019)
10.1111/febs.14934
TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells
K. Schoeler (2019)
10.1016/j.immuni.2019.09.003
Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells.
E. H. Ma (2019)
10.1093/intimm/dxz008
Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression.
Hiroko Nakatsukasa (2019)
10.1016/j.celrep.2019.01.070
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
G. Garg (2019)
10.1128/IAI.00677-19
l-Serine Lowers the Inflammatory Responses during Pasteurella multocida Infection
Fang He (2019)
10.12688/f1000research.17358.1
New insights emerge as antibody repertoire diversification meets chromosome conformation
A. Kenter (2019)
10.1038/s41577-019-0151-6
Epigenetic regulation of the innate immune response to infection
Q. Zhang (2019)
10.1039/c8an01581c
Advances in mass spectrometry based single-cell metabolomics.
K. D. Duncan (2019)
10.1038/s41467-019-09541-y
Loss of TET2 and TET3 in regulatory T cells unleashes effector function
X. Yue (2019)
10.1016/j.cmet.2019.01.014
Serine Metabolism Supports Macrophage IL-1β Production.
Arianne E. Rodriguez (2019)
10.1146/annurev-animal-020518-115206
One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development.
Constance E Clare (2019)
ine metabolism supports macrophage IL - 1 b production
AE Rodriguez (2019)
10.1002/art.41208
Methionine Commits Cells to Differentiate Into Plasmablasts Through Epigenetic Regulation of BTB and CNC Homolog 2 by the Methyltransferase EZH2
Mingzeng Zhang (2020)
10.1038/s41467-019-13668-3
Mitochondrial TCA cycle metabolites control physiology and disease
I. Martínez-Reyes (2020)
10.1016/j.cmet.2020.01.006
Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming.
D. Roy (2020)
10.1007/s12038-019-9973-4
TET methylcytosine oxidases: new insights from a decade of research
C. Lio (2020)
Methionine commits cells to differentiate into plasmablasts through epigenetic regulation of BTB and CNC homolog 2 by the methyltransferase enhancer of zeste homolog
M Zhang (2020)
Methionine commits cells to differentiate into plasmablasts through epigenetic regulation of BTB and CNC homolog 2 by the methyltransferase enhancer of zeste homolog 2
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Clinical Applications and Properties of Calcium Citrate Malate C Research
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10.1111/imm.13301
Sweet talk: Metabolic conversations between host and microbe during infection
Eyal Amiel (2021)
10.1111/imr.13045
Micro but mighty-Micronutrients in the epigenetic regulation of adaptive immune responses.
(2021)
10.1016/j.jid.2020.10.012
Role of Epigenetics in the Regulation of Immune Functions of the Skin.
Y. Sawada (2020)
10.3390/metabo10100394
Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape
Haoxin Zhao (2020)
10.1101/2020.11.12.380626
SAM homeostasis is regulated by CFIm-mediated splicing of MAT2A
Anna M Scarborough (2020)
10.1016/j.freeradbiomed.2020.11.016
Mitochondria signaling to the epigenome: a novel role for an old organelle.
J. Santos (2020)
10.1111/imm.13275
Metabolic mediators: How immunometabolism directs the immune response to infection
Eyal Amiel (2020)
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