Epigenetics of the Immune System (Volume 16) (Translational Epigenetics (Volume 16))

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Contributors
Preface
An introduction to immunology and epigenetics
	Development of immune cells
	Dynamics of the immune response
	Immunological memory
	Basic overview of epigenetic regulation
	Genome architecture at primary structure scale: Cis-regulation through DNA elements
	Genome architecture at secondary structure scale: Trans-regulation through chromatin packaging and nucleosome positioning
	Genome architecture at tertiary structure scale: Long-range chromatic interactions and gene regulation within chromatin ter ...
	Posttranscriptional regulation of RNA expression
	Posttranslational modifications: Chromatin remodeling complexes and histones
	Posttranslational modifications: Nonhistone proteins
	Advancing technology and use of interdisciplinary approaches
	References
Plant epigenetics and the `intelligent´ priming system to combat biotic stress
	Introduction
	Plant DNA methylation
	De novo DNA methylation
	Maintenance DNA methylation
	Histone modifications
	RNA-associated silencing
	Epigenetics of plant microbe interactions
	Epigenetics of plant insect interactions
	Epigenetics of immune system and memory in plants
	Plant epigenetics: Model plants and application in agriculture
	Somatic embryogenesis
	Heterosis
	Conclusions
	References
Understanding immune system development: An epigenetic perspective
	Introduction: An outline of the chapter
	Epigenetic modifications and their functional output
		Transcriptional control of epigenetic modifications: From on/off to cycling of epigenetic modifications
		DNA methylation: The mark of silence
		Histone modifications: Key epigenetic drivers
		Interdependence of DNA and histone modifications
		Epigenetic modifications mediated by chromatin remodeling and noncoding RNA (ncRNA)
		Accessible chromatin: A prelude to transcription
		Poised state of a gene: Epigenetic modifications priming gene for activation
	Epigenetic mechanisms regulating immune cell development
		Epigenetic regulation during hematopoiesis
		Development of innate immune cells: Regulation by epigenetic processes
			Development of natural killer (NK) cells
			ILC2 cell development
			Development of macrophages
			Development of dendritic cells
				Transcription factors and epigenetic mechanisms involved in DC development
		Epigenetic mechanisms in adaptive immune system
			B-cell development and differentiation-An epigenetic perspective
				Pro-B to pre-B cell commitment
				Pre-B to immature B cells-Formation of BCR
				Peripheral differentiation of B cells
			Role of epigenetic regulation in T cells
				From CLPs to T cells-Regulation by transcription factors and epigenetic modifications
				CD4/CD8 lineage commitment: The epigenetic contribution
				Terminal differentiation and function of T cells in the periphery
				Epigenetic changes in T-cell plasticity and memory
			Gene regulation by long-distance interactions
	Concluding remarks and future perspective
	References
	Further reading
Epigenetic mechanisms in the regulation of lymphocyte differentiation
	Introduction
	Part I: Chromatin-based epigenetic mechanisms in lymphocyte differentiation
		DNA methylation and lineage commitment
		DNA methylation writers, readers, and erasers in immune cell differentiation
		Histone modifications in lymphocyte differentiation
		Histone modification writers, readers, and erasers in lymphocyte differentiation
		Chromatin accessibility in the differentiation of immune cells
	Part II: RNA-based mechanisms of regulation of lymphocyte differentiation
		MicroRNA-mediated regulation of T- and B-cell differentiation
		Specific miRNAs regulating T- and B-cell differentiation
		The emerging role of lncRNAs in immune cell differentiation
		LncRNAs in T-cell differentiation
		LncRNAs in B-cell differentiation
		Cross talk between noncoding RNAs
	Concluding remarks
	References
	Further reading
Epigenetics mechanisms driving immune memory cell differentiation and function
	Introduction
	Functional heterogeneity within the memory T-cell pool
	Histone methylation and pattern, acquisition of function
	DNA methylation and its role in regulating gene transcription
		Making sense of the ``junk DNA´´: Noncoding regulatory elements work via chromatin folding
	Epigenetic regulation in the acquisition of lineage-specific T-cell function
	Epigenetic regulation in the acquisition of CD8 T-cell function
	Epigenetic mapping of the differentiation pathway that leads to T-cell memory
	The role of CD8+ T-cell-specific transcription factors in chromatin remodeling and acquisition of function
	Active regulation of chromatin state is a key factor in CD8+ T-cell effector vs memory fate decisions
	Conclusion
	References
Microbiota in the context of epigenetics of the immune system
	Introduction
	Epigenetic mechanisms
	Gut microbiome and epigenetics of immune cells
		Gut microbiota and epigenetics of Treg cells
		Gut microbiota and epigenetics of mononuclear phagocytes
		Gut microbiota and epigenetics of ILCs
		Gut microbiota and iNKT cells
	Skin microbiota and epigenetics of immune cells
	Microbiome and epigenetics of nonmucosal immune cells
		Microbiota and nonmucosal myeloid cells
		The case of SCFA
		The case of folate
		Epigenetic imprint of microbes on offspring's immune cells
	Conclusions and prospects
	References
Sequencing technologies for epigenetics: From basics to applications
	Introduction to high-throughput sequencing
		Next-generation sequencing
			Illumina sequencing protocol
	Library preparation
	Flow cell preparation
	Sequencing by synthesis
		Third-generation sequencing
			Nanopore sequencing
			SMRT sequencing
	Applications of sequencing technologies for epigenetics
		DNA methylation
		Histone modifications
		Other applications
	Data processing and computational analysis
		Raw data and quality control
		Read alignment
		Analysis of methylation data
			DNA methylation scoring
			Differential methylation
			Methylome segmentation
		Analysis of ChIP-seq data
			Quality control of ChIP-seq data
		Analysis of data from other applications
	Future perspectives
	References
Advances in single-cell epigenomics of the immune system
	Introduction
	Single-cell epigenomics technologies
		DNA modifications
		Protein-DNA interaction
	Chromatin structure
		Chromosome conformation
		Single-cell multiomics
	Computational challenges and solutions
		Quality control and preprocessing
		Downstream analysis
	Studying the immune system using single-cell epigenomics
		Hematopoiesis
		Leukemia
		Aging
	Conclusions and future perspectives
		Single-cell epigenomics with a spatial resolution
		Other future applications
	References
Machine learning and deep learning for the advancement of epigenomics
	The ``epigenetic code´´ problem
	Progress of machine learning: Classification versus non-supervised learninga
	Unsupervised approaches
	Supervised approaches
		Methods for training data generation
		Classical classification methods
			Prediction of enhancer regulatory state with Bayesian networks
			Multiple kernel learning approach for the identification of tissue specific developmental enhancers
			Prediction of active enhancers based on DNA methylation marks and histone modifications with random forest classifier
		New approaches-Deep learning
	Conclusion
	References
Systems immunology meets epigenetics
	Epigenetic modifications within the immune system
		DNA methylation
		RNA modification
		Histone modifications
	Systems approach for deconvoluting immune cell composition
		Deconvolution frameworks
		Reference-based models
		Reference-free models
		Perspectives
	References
Epigenetic deregulation of immune cells in autoimmune and autoinflammatory diseases
	Relevance of epigenetics for immune deregulation in autoimmune/autoinflammatory disorders
	Epigenetic dysregulation in autoimmune diseases
		Epigenetic defects of immune cells in rheumatoid arthritis
		Epigenetic defects of immune cells in psoriasis
	Epigenetic dysregulation in autoinflammatory diseases
		Familial Mediterranean fever
		Cryopyrin-associated periodic syndromes
	Epigenetic biomarkers in autoimmunity
	Targeting epigenetic defects
	References
Epigenetics of allergies: From birth to childhood
	Neonatal DNA methylation profiles as predictors of the trajectory to asthma and allergy
	DNA methylation profiles in patients with childhood asthma and allergy
		DNA methylation in the airways
	What have we learned so far?
	References
Epigenetic regulation of normal hematopoiesis and its dysregulation in hematopoietic malignancies
	Epigenetic regulation of normal hematopoiesis
		Epigenetic modifications
		Cis-regulatory elements
		Normal hematopoiesis
		Epigenome dynamics during normal hematopoietic differentiation
	Mutations of epigenetic regulators in clonal hematopoiesis and in hematopoietic neoplasms
		Preleukemic mutations
		Mutations in myeloid neoplasms
	Epigenetic deregulation in T-cell acute lymphoblastic leukemia
		Leukemogenesis of T-ALL
		Alterations in epigenetic modifiers
		Methylation profiles in T-ALL
		Deregulation of the TAL1 oncogene: A model for enhancer hijacking and oncogenic neo-enhancers
		Oncogenic neo-enhancers deregulating T-ALL oncogenes
	Cell-of-origin identification using epigenetics: Chronic lymphocytic leukemia as a model
		Epigenetically deregulated genes as biomarkers in CLL
		Methylomics identify CLL subgroups of different cellular origins
		Identification of disease-specific DNA methylation patterns in CLL
	Epigenomics for disease classification and as a diagnostic tool
		Epigenetic biomarkers
		DNA methylation biomarkers for cancer classification and risk assessment
		Computational models for cancer classification
	Epigenetic therapies in hematopoietic neoplasms
		Inhibitors of epigenetic key players
		Mechanisms of epigenetic therapies and possible rationales for drug combinations
	References
Impact of epigenetic modifiers on the immune system
	Overview
	Epigenetic modifiers
		HDAC inhibitors
		HAT inhibitors
		DNMT inhibitors
		BET inhibitors
		EZH2 inhibitors
		LSD1 inhibitors
		DOT1L inhibitors
	Immunomodulatory effects of epigenetic modifiers
		Effect of HDACi on immune cells
			T cells
			Regulatory T (Treg) cells
			B cells
			Myeloid-derived suppressor cells
			Antigen-presenting cells
			Macrophages
			Dendritic cells
		Effect of DNMTi on immune cells
			T cells
			Treg cells
			B cells
			Macrophages
			Dendritic cells
	Clinical significance of epigenetic modifiers
		HDACi therapy
		DNMTi therapy
		Other epigenetic modifiers in therapy
	Combination therapy involving epigenetic modifiers
		Epigenetic modifiers and immunotherapy
		Epigenetic modifiers and chemotherapeutics
		Epigenetic modifiers and radiotherapy
		Combination therapy with HDACi and DNMTi
	Conclusion
	References
Index
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