Table 1.
Chromatin modifiers with possible relevance for lymphoma: an overview.
| 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 |
1: Epigenetic writers add the covalent modification to either histone tails or the DNA. Here we consider only histone lysine methyltransferases (KMTs) and DNA methyltransferases (DNMTs). Epigenetic erasers catalyze the removal of epigenetic marks, e.g., to alter gene expression. Here we consider only histone lysine (KDMs) and DNA (DNDMs) demethylases. Epigenetic readers possess effector domains and recognize and bind to modified residues. Many “classical” transcription factors (that “read” special DNA binding motifs) are also epigenetic readers because their binding to DNA is also governed by epigenetic marks (see also [1,48] and Figure 1b); 2: expected net effect on the transcriptional activity of the affected genes. In general there is no one-to-one relation between a certain epigenetic modifier and the change of gene expression. Combinations of modifiers and their marks give rise to a large variety of options (called also chromatin code). Here we assign the proposed effects of chromatin marks on gene expression according to GeneCards (www.genecards.org); 3: activating/gain of function (+) or deactivating/loss of function (x) mutation observed in lymphoma; 4: differential expression with respect to B cells: +…up; − …down; x…indifferent; 5: spot cluster: e.g., A… gene belongs to spot A; (A)…gene is found near spot A in the map; spot characteristics: B,C,D: up in BL and down in DLBCL/FL; F: up in FL; I: up in BCL and MM and down in BL and partly DLBCL; J: up in B and GCB cells and down in lymphoma; H: up in B cells, tonsils and FL, down in BL; 6: mutation data and assignments to lymphoma classes were taken from [28,29,30,31,32]; *: enzymes marked with asterisks perform multiple roles by catalyzing more than one lysine side chain.