histone-lysine N-methyltransferase SUV39H1; histone H3-K9 methyltransferase 1; H3-K9-HMTase 1; lysine N-methyltransferase 1A; position-effect variegation 3-9 homolog; suppressor of variegation 3-9 homolog 1; Su(var)3-9 homolog 1 (SUV39H1, KMT1A, SUV39H)
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Function
- histone methyltransferase
- specifically trimethylates Lys-9 of histone H3 using monomethylated H3 Lys-9 as substrate
- also weakly methylates histone H1 (in vitro)
- H3 Lys-9 trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 &/or CBX5) proteins to methylated histones
- functions in heterochromatin regions, thus playing a role in establishment of constitutive heterochromatin at pericentric & telomere regions
- H3 Lys-9 trimethylation is also required to direct DNA methylation at pericentric repeats
- SUV39H1 is targeted to histone H3 via its interaction with RB1 & is involved in many processes, including
- repression of MYOD1-stimulated differentiation
- regulating exiting of the cell cycle & entering differentiation
- repression by the PML-RARA fusion protein
- BMP-induced repression
- repression of switch recombination to IgA
- regulation of telomere length
- component of the eNoSC complex
- negatively regulated by KIAA1967/DBC1
- phosphorylated on Ser, & to a lesser degree, on Thr
- the phosphorylated form is stabilized by SBF1 & is less active in its transcriptional repressor function
- acetylated at Lys-266, leading to inhibition of enzyme activity
- SIRT1-mediated deacetylation relieves this inhibition
- interacts with H3 & H4 histones
- interacts with GFI1B, DNMT3B, CBX1, CBX4, KIAA1967/DBC1, MBD1, RUNX1, RUNX3, MYOD1, SMAD5 & RB1
- interacts with SBF1 through the SET domain
- interacts with HDAC1 & HDAC2 through the N-terminus & associates with the core histone deacetylase complex composed of HDAC1, HDAC2, RBBP4 & RBBP7
- in case of infection, interacts with HTLV-1 Tax protein, leading to abrogate Tax transactivation of HTLV-1 LTR
- interacts (via SET domain) with MECOM; e nhances MECOM transcriptional repression activity , S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]
Inhibition:
- inhibited by S-adenosyl-L-homocysteine
Structure
- although the SET domain contains the active site of enzymatic activity, both pre-SET & post-SET domains are required for methyltransferase activity
- the SET domain also participates in stable binding to heterochromatin
- belongs to the histone-lysine methyltransferase family, Suvar3-9 subfamily
- contains 1 chromo domain
- contains 1 post-SET domain
- contains 1 pre-SET domain
- contains 1 SET domain
Compartment
- nucleus, chromosome, centromere
- associates with centromeric constitutive heterochromatin
Expression
- accumulates during mitosis at centromeres during prometaphase, but dissociates from the centromere at the metaphase to anaphase transition