Histone Mutations and Cancer

Acknowledgement
Contents
Chapter 1: Overview of Histone Modification
	1.1 Histone Methylation
		1.1.1 H3K4 Methylation
		1.1.2 H3K9 Methylation
		1.1.3 H3K27 Methylation
		1.1.4 H3K36 Methylation
		1.1.5 H3K79 Methylation
		1.1.6 H4K20 Methylation
	1.2 Histone Acetylation
	1.3 Histone Phosphorylation
	1.4 Chromatin Remodeler
	1.5 Non-coding RNA
	References
Chapter 2: The Histone H3 Family and Its Deposition Pathways
	2.1 Introduction
		2.1.1 Chromatin
		2.1.2 Histones
		2.1.3 Replicative Histones and Histone Variants
	2.2 The Histone H3 Family
		2.2.1 Replicative H3.1 and H3.2
		2.2.2 H3.3 Variant
		2.2.3 CenH3CENP-A Variant
	2.3 Histone H3-H4 Chaperones
		2.3.1 Histone Chaperone Definition
		2.3.2 Dedicated H3-H4 Chaperones
			2.3.2.1 H3.1/2-H4 Chaperone
			2.3.2.2 H3.3-H4 Chaperones
			2.3.2.3 CenH3CENP-A-H4 Chaperone
		2.3.3 Other H3-H4 Chaperones
	2.4 Deposition of H3-H4 Histones onto DNA
		2.4.1 Deposition of New H3-H4 Histones
			2.4.1.1 New H3.1/2-H4 Deposition by CAF-1
			2.4.1.2 New H3.3-H4 Deposition by HIRA
			2.4.1.3 New H3.3-H4 Deposition by DAXX-ATRX
			2.4.1.4 New CenH3CENP-A-H4 Deposition by HJURP
		2.4.2 Recycling of Old H3-H4 Histones
	2.5 Concluding Remarks and Perspectives
	References
Chapter 3: Histone H3K27M Mutation in Brain Tumors
	3.1 Introduction
	3.2 Role of Oncohistones H3.1K27M and H3.3K27M in Brain Tumors
	3.3 Role of H3K27me3 Landscape Changes in Reprogramed Epigenome and Gene Expression in Brain Tumors
	3.4 Involvement of H3K27ac Gain in the Epigenetic Landscape Changes in Brain Tumors
	3.5 Influence of H3K27M and H3K27me3 Alterations on the Gene Expression in Brain Tumors
	3.6 Different H3K27M-Driven Tumorigenic Mechanisms and Their Impacts on the Epigenome
	3.7 Other H3K27M-Driven Tumorigenic Mechanisms in the Brain
	3.8 H3K27M-DIPG Therapeutic Approaches and Strategies
		3.8.1 The Reverse of H3K27ac Gain Approach
		3.8.2 The Rescue of H3K27me3 Approach
		3.8.3 Targeting the Activities of Residual EZH2 Approach
	3.9 Conclusion, Perspective, and Future Direction
	References
Chapter 4: Histone Mutations and Bone Cancers
	4.1 Introduction
	4.2 Bone Development, Homeostasis, and Bone Tumors
	4.3 Histones and Epigenetics
		4.3.1 Lysine Methylation of Histones
		4.3.2 Nuclear Receptor SET Domain-Containing (NSD) Methyltransferase 2
		4.3.3 Su(Var)3-9, Enhancer of Zeste, Trithorax Domain-Containing (SETD) Methyltransferase 2
	4.4 Histone Mutations in Bone Tumors
		4.4.1 Chondroblastomas
		4.4.2 Giant Cell Tumors of Bone (GCTB)
		4.4.3 Other Bone Tumors
	4.5 Therapeutic Opportunities for Bone Tumors Harboring Oncohistones
	4.6 Conclusion and Perspectives
	References
Chapter 5: Histone H3G34 Mutation in Brain and Bone Tumors
	5.1 Oncohistone H3G34R/V Mutation in Brain Tumors
	5.2 Oncohistone H3G34W/L Mutation in Bone Tumors
	5.3 Impact of H3G34 Mutation on the Epigenome
	5.4 H3G34 Mutation and Genomic Instability
	References
Chapter 6: Epigenetic-Targeted Treatments for H3K27M-Mutant Midline Gliomas
	6.1 Introduction
	6.2 The Histone and Epigenetic Landscape
	6.3 H3K27M and Lysine Methylation
		6.3.1 Molecular Biology of Lysine Methylation
		6.3.2 Targeting Methylation
			6.3.2.1 Demethylase Inhibition
			6.3.2.2 Methyltransferase Inhibition
	6.4 H3K27M and Acetylation
		6.4.1 Molecular Biology of Lysine Acetylation
		6.4.2 Targeting Acetylation
			6.4.2.1 HDAC Inhibition
			6.4.2.2 BET Inhibition
	6.5 H3K27M and Phosphorylation
	6.6 Future Considerations
	6.7 Conclusions
	References
Chapter 7: Histone Lysine-to-Methionine Mutation as Anticancer Drug Target
	7.1 Introduction
	7.2 Posttranscriptional Modifications of Histones
	7.3 Histone H3 Mutations in Cancer
	7.4 Histone Lysine 27 to Methionine Mutation
	7.5 Mechanistic Insights into the Role of H3K27M
	7.6 Histone Lysine 36 to Methionine Mutation
	7.7 Therapeutic Targeting of Histone Lysine-to-Methionine Mutation
	7.8 The Targeting Strategies for H3.3K27M
	7.9 The Targeting Strategies for H3.3K36M
	7.10 Conclusion and Perspective
	References