Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers
Abstract
:1. Introduction
2. Data and Methods
2.1. Lymphoma Gene Expression Data
2.2. High-Dimensional Data Portraying
2.3. Pathway Signal Flow (PSF) Analysis
3. Results and Discussion
3.1. Transcription and DNA Methylation under the Control of Epigenetic Modifiers
3.1.1. Mutual Coupling of Writer/Eraser Activities
3.1.2. Mutations of EZH2 and MLL2 Potentially Induce Hypermethylation
3.1.3. Epigenetics under Metabolic Control
Target | Type1 | Enzyme | Alias | Mark | txn2 | mut3 | DEx4 | Spot5 | Comment6 |
---|---|---|---|---|---|---|---|---|---|
Writer Eraser Reader | Me | act. repr. | LvsBc4 | ||||||
H3K4 | W | KMT2A | MLL | act | − | IJ | TrxG:MLL complex | ||
KMT2B | MLL2, KMT2D | act | x | − | J | loss of function in DLBCL/FL, TrxG:MLL complex | |||
KMT2F | SETD1A | act | − | (H) | |||||
KMT2G | SETD1B | Me3 | act | − | H | ||||
KMT3C * | SMYD2 | Me2/Me3 | act | x | (MM) | ||||
KMT3E | SMYD3 | Me2/Me3 | act | + | (D) | ||||
PRDM9 | MSBP3. PFM6 | Me3 | act | − | (I) | ||||
SETMAR * | METNASE | act | x | B | |||||
E | KDM1A * | LSD1, AOF2 | Me1/Me2 | rep | + | B | “gene body cleaner” | ||
KDM5A | JARID1A, RBBP2 | Me2/Me3 | rep | x | (A) | JmjC, “gene body cleaner” | |||
KDM5B | JARID1B, PLU1 | rep | − | (F) | JmjC | ||||
KDM5C | JARID1C, SMCX | rep | + | (I) | JmjC | ||||
H3K9 | W | KMT1C * | EHMT2, G9A | Me1/Me2 | rep | x | (B) | ||
KMT1D * | EHMT1, GLP | Me1/Me2 | rep | + | (D) | ||||
KMT1E | SETDB1 | Me3 | rep | x | (I) | ||||
KMT6(A) * | EZH2 | rep | + | + | D | gain of function in cancer/DLBCL/FL, PRC2 complex | |||
KMT8 | PRDM2, RIZ | rep | − | (D) | Missense mutation in DLBCL | ||||
E | KDM1A * | LSD1, AOF2 | act | + | B | ||||
KDM3A | JMJD1, TSGA | Me1/Me2 | act | − | (IM) | JmjC | |||
KDM3B | JHDM2B | act | x | (C) | JmjC | ||||
KDM4A * | JMJD2 | Me3 | act | − | (J) | JmjC | |||
KDM4B | JHDM3B | Me3 | act | − | J | JmjC | |||
KDM4C * | JHDM3C | Me3 | act | − | I | JmjC | |||
KDM4D | JMJD2D | Me2/Me3 | act | x | (B) | JmjC | |||
KDM7A * | JHDM1D | Me2 | act | − | H | JmjC | |||
MINA | MDIG, ROX | Me3 | act | + | (B) | ||||
H3K27 | W | KMT1C * | EHMT2, G9A | rep | x | (B) | |||
KMT1D * | EHMT1, GLP | rep | + | (D) | |||||
KMT6(A) * | EZH2 | rep | + | + | D | gain of function in cancer/DLBCL/FL, PRC2 complex | |||
KMT6B | EZH1 | rep | − | J | PRC2 complex | ||||
WHSC1 | NSD2, MMSET | rep | + | D | mutated in BL and MCL, opens chromatin | ||||
E | KDM6A | UTX | Me2/Me3 | act | − | (IM) | |||
KDM6B | JMJD3 | Me2/Me3 | act | − | J | involved in inflamma-tory response, JmjC | |||
KDM7A * | JHDM1D | Me2 | act | x | − | H | JmjC | ||
H3K36 | E | KDM2A | FBXL11, JHDM1A | Me2 | − | (H) | JmjC | ||
KDM4A * | JMJD2 | Me3 | rep | − | (J) | JmjC | |||
KDM4C * | JHDM3C | Me3 | rep | − | I | JmjC | |||
KDM8 | JMJD5 | Me2 | rep | x | (B) | JmjC | |||
W | KMT2H | ASH1L | act | − | (I) | ||||
KMT3A | SETD2, SET2 | Me3 | act | − | J | recruits MMR | |||
KMT3B | NSD1, STO | − | (J) | ||||||
KMT3C * | SMYD2 | Me2 | act | x | (MM) | ||||
SETMAR * | METNASE | Me2 | act | x | B | ||||
H3K79 | W | KMT4 | DOT1L | act | x | x | (MM) | Loss of function in Lymphoma | |
DNA | W | DNMT1 | rep | + | D | maintenance | |||
DNMT3A | rep | x | (D) | de novo methylation | |||||
DNMT3B | rep | + | B | de novo methylation | |||||
DNMT3L | rep | + | (D) | Induces de novo DNA methylation by recruitment or activation of DNMT3 | |||||
E | TET3 | act | − | I | |||||
R, E | MBD2 | act/rep | − | (I) | mediates CpG-methylation signal |
3.2. Expression Cartography of Epigenetic Modifiers
3.2.1. SOM Expression Map of Epigenetic Modifiers
3.2.2. DNA Methylating Enzymes: DNA-MTs and -DMs
3.2.3. Histone K27MTs and DMs
3.2.4. Histone K4MTs and DMs
3.2.5. Histone K9MTs and DMs
3.2.6. Histone K36MTs and DMs
3.2.7. Histone K79MT
3.3. Expression Cartography of Chromatin Remodeling Complexes
3.3.1. TrxG/MLL Complex
3.3.2. PRC1 Complex
3.3.3. PRC2 Complex
3.3.4. SWI/SWF Complex
3.4. Energy Metabolism Couples with Epigenetics in Lymphoma?
3.5. Deregulation of Epigenetic Modifiers Governs Heterogeneity of Lymphoma
3.5.1. Dysregulation of Epigenetic Writer-Eraser Equilibria Diminish Plasticity of B Cells during Maturation
3.5.2. Activation of Gene Expression and of TCA Metabolism in Lymphoma Associates with Epigenetics
3.5.3. Asymmetric Activation of Methyl-Writers and -Erasers
4. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Hopp, L.; Nersisyan, L.; Löffler-Wirth, H.; Arakelyan, A.; Binder, H. Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers. Genes 2015, 6, 1076-1112. https://doi.org/10.3390/genes6041076
Hopp L, Nersisyan L, Löffler-Wirth H, Arakelyan A, Binder H. Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers. Genes. 2015; 6(4):1076-1112. https://doi.org/10.3390/genes6041076
Chicago/Turabian StyleHopp, Lydia, Lilit Nersisyan, Henry Löffler-Wirth, Arsen Arakelyan, and Hans Binder. 2015. "Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers" Genes 6, no. 4: 1076-1112. https://doi.org/10.3390/genes6041076
APA StyleHopp, L., Nersisyan, L., Löffler-Wirth, H., Arakelyan, A., & Binder, H. (2015). Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers. Genes, 6(4), 1076-1112. https://doi.org/10.3390/genes6041076