Table 1.

Abnormalities of histone methylation identified in myelodysplastic syndromes: histone methyltransferases, histone demethylases and their associated gene products in myelodysplastic syndromes.

Modified residue	HMT/HDM involved in MDS	Defect of HMT/HDM in MDS	Defect of targets/interacting proteins of HMT/HDM in MDS	Inhibitor
Activating K methylation
H3K4	MLL (HMT); LSD1 (HDM)	Gene amplification (rare)	HoxA9, Meis1 (possible targets of MLL): overexpressed in MDS LSD1 interacting proteins; GFI1: overexpressed in high-risk MDS; TAL1: upregulated in SDS syndrome; ASXL1: loss of function mutation in MDS	Several MAO inhibitor derivatives
H3K36	NSD1/3 (HMT); JHDM1A/B (HDM)	NUP98–NS1/3 fusion	HoxA9 (possible target of NSD1): overexpressed in MDS; BCL6 (interact with JHDM1a/b): amplification of BCL6 gene in MDS
H3K79	DOT1L (HMT)		MLL–AF4 fusion (interact with DOT1L): gene fusion in MDS rare); targets of DOT1L: GATA2: overexpressed in MDS; PU.1: interacting with EVI1
Repressive K methylation
H3K27	EZH2 (HMT); UTX (HDM); JMJD3 (HDM)	Mutation/overexpression in MDS; mutations in MDS	p16INK4 (target of JMJD3): overexpressed in MDS but not AML	DZNep
H3K9	SUV39H1 (HMT); G9A (HMT)		EVI1 (interacting protein of SUV39H1 and G9a): overexpressed in MDS; p15INK4b and E-cadherin (targets of SUV39H1): silencing in MDS
H4K20		Level increase in Arid4a/4b KO mice, which have defects that progress into MDS and AML
R methylation
H4R3	PRMT1	PRMT1 enhances self-renewal of hematopoietic cells	MLL	AMI-1 derivatives, RM65
H3R2	PRMT6	PRMT6 inhibits MLL mediated H3K4 methylation	Chaetocin, BIX-01294

AMI-1: Arginine methyltransferase inhibitor 1; AML: Acute myelogenous leukemia; DZNep: 3-deazaneplanocin A; HDM: Histone demethylases; HMT: Histone methyltransferases; K: Lysine residue; KO: Knockout; MAO: Monoamine oxidase; MDS: Myelodysplastic syndromes; MLL: Mixed-lineage leukemia; PRMT: Protein arginine methyltransferases; R: Arginine residue.