Histone lysine methylation

Methylation is one of the most well studied modifications on histones. Lysine residues in histones can undergo mono (me1), di (me2) and trimethylation (me3). These modifications are carried out by a category of enzymes called 'lysine methyltrasferases'. The methyl donor in this case is S-Adenosyl methionine (SAM). Methylation does not change the charge on histone proteins and hence its interaction with DNA is not affected. Each methyl moiety adds ~14 daltons to the histone proteins.

Histone methylation marks are highly specific i.e. their downstream effect on the gene expression is dependent on the site and extent of methylation. Methylation of lysine residues present at position 4 and 36 strictly associate with transcriptional activation whereas residues on 9 and 27 lead to transcriptional repression. Such specific modifications can help differentiate between euchromatin and heterochromatin. Monomethylation often acts as a substrate for enzymes that further catalyse di and trimethylation of the same residue. Among the compiled list we find relatively few enzymes that catalyse complete (mono, di and tri) methylation of a given residue. Studies on prominent histone active (H3K4me3) and repressive (H3K27me3) methylation marks have proposed the concept of 'Bivalent chromatin domains' as gene rich regions that harbour both these marks and hence are poised for transcriptional activation or repression.


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Sites of histone lysine methylation
Site of modification Writers Erasers
H1K186me1 Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, Histone-lysine N-methyltransferase, H3 lysine-9 specific 5
H1K25me1 Histone-lysine N-methyltransferase EZH2, Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, Histone-lysine N-methyltransferase, H3 lysine-9 specific 5 Lysine-specific demethylase 4D
H2BK5me1
H3K27me1 Histone-lysine N-methyltransferase EZH1, Histone-lysine N-methyltransferase EZH2, Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, Histone-lysine N-methyltransferase, H3 lysine-9 specific 5
H3K27me2 Histone-lysine N-methyltransferase EZH1, Histone-lysine N-methyltransferase EZH2, Histone-lysine N-methyltransferase NSD3 Histone lysine demethylase PHF8, Lysine-specific demethylase 6B, Lysine-specific demethylase 7
H3K27me3 Histone-lysine N-methyltransferase EZH2, Histone-lysine N-methyltransferase NSD3 Lysine-specific demethylase 6A, Lysine-specific demethylase 6B
H3K36me1 Probable histone-lysine N-methyltransferase ASH1L
H3K36me2 Histone-lysine N-methyltransferase SETMAR, Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific, N-lysine methyltransferase SMYD2, Probable histone-lysine N-methyltransferase ASH1L Lysine-specific demethylase 2A, Lysine-specific demethylase 2B, Lysine-specific demethylase 8
H3K36me3 Histone-lysine N-methyltransferase SETD2, Probable histone-lysine N-methyltransferase NSD2 Lysine-specific demethylase 4A, Lysine-specific demethylase NO66
H3K4me1 Histone-lysine N-methyltransferase SETD7 Lysine-specific histone demethylase 1A
H3K4me2 Histone-lysine N-methyltransferase NSD3 Lysine-specific demethylase 5A, Lysine-specific demethylase 5D, Lysine-specific histone demethylase 1A
H3K4me3 Histone-lysine N-methyltransferase MLL, Histone-lysine N-methyltransferase MLL3, Histone-lysine N-methyltransferase MLL4, Histone-lysine N-methyltransferase PRDM9, Histone-lysine N-methyltransferase SETD1A, Histone-lysine N-methyltransferase SETD1B, SET and MYND domain-containing protein 3 Histone lysine demethylase PHF8, Lysine-specific demethylase 2B, Lysine-specific demethylase 5A, Lysine-specific demethylase 5B, Lysine-specific demethylase 5C, Lysine-specific demethylase 5D, Lysine-specific demethylase NO66
H3K79me1 Histone-lysine N-methyltransferase, H3 lysine-79 specific
H3K79me2 Histone-lysine N-methyltransferase, H3 lysine-79 specific
H3K79me3 Histone-lysine N-methyltransferase, H3 lysine-79 specific
H3K9me1 Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Lysine-specific demethylase 3A, Lysine-specific demethylase 3B, Lysine-specific histone demethylase 1A
H3K9me2 Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, Histone-lysine N-methyltransferase, H3 lysine-9 specific 5, PR domain zinc finger protein 2 Histone lysine demethylase PHF8, Lysine-specific demethylase 3A, Lysine-specific demethylase 3B, Lysine-specific demethylase 4C, Lysine-specific demethylase 4D, Lysine-specific demethylase 7, Lysine-specific histone demethylase 1A, Lysine-specific histone demethylase 1B
H3K9me3 Histone-lysine N-methyltransferase SETDB1, Histone-lysine N-methyltransferase SETDB2, Histone-lysine N-methyltransferase SUV39H1, Histone-lysine N-methyltransferase SUV39H2 Lysine-specific demethylase 4A, Lysine-specific demethylase 4B, Lysine-specific demethylase 4C, Lysine-specific demethylase 4D
H4K20me1 Histone-lysine N-methyltransferase SETD8, Probable histone-lysine N-methyltransferase NSD2 Histone lysine demethylase PHF8
H4K20me2 Histone-lysine N-methyltransferase SETD8, Histone-lysine N-methyltransferase SUV420H1, Histone-lysine N-methyltransferase SUV420H2, Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific
H4K20me3 Histone-lysine N-methyltransferase SUV420H1, Histone-lysine N-methyltransferase SUV420H2, Probable histone-lysine N-methyltransferase NSD2