SUV39H1
Description
The SUV39H1 (SUV39H1 histone lysine methyltransferase) is a protein-coding gene located on chromosome X.
SUV39H1 is a member of the suppressor of variegation 3-9 homolog family and encodes a protein with a chromodomain and a C-terminal SET domain. This nuclear protein moves to the centromeres during mitosis and functions as a histone methyltransferase, methylating lysine-9 of histone H3. Overall, it plays a vital role in heterochromatin organization, chromosome segregation, and mitotic progression.
SUV39H1 is a histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3, using monomethylated H3 'Lys-9' as a substrate. It also weakly methylates histone H1 (in vitro). Trimethylation of H3 'Lys-9' acts as a tag for epigenetic transcriptional repression by attracting HP1 (CBX1, CBX3, and/or CBX5) proteins to the methylated histones. Primarily functioning in heterochromatin regions, SUV39H1 plays a crucial role in establishing constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also essential for directing DNA methylation at pericentric repeats. SUV39H1's interaction with RB1 targets it to histone H3, and it participates in various processes, including repression of MYOD1-stimulated differentiation, regulation of the cell cycle exit and entry into differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, suppression of switch recombination to IgA, and regulation of telomere length. SUV39H1 is a component of the eNoSC (energy-dependent nucleolar silencing) complex, which silences rDNA in response to intracellular energy status by recruiting histone-modifying enzymes. The eNoSC complex senses the cell's energy status: upon glucose starvation, the increased NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. The large PER complex recruits SUV39H1 to E-box elements in circadian target genes like PER2 and PER1, contributing to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.
SUV39H1 is also known as H3-K9-HMTase 1, KMT1A, MG44, SUV39H.
Associated Diseases
- endometrial cancer
- breast cancer
- nonpapillary renal cell carcinoma
- leukemia, acute, X-linked
- limb ischemia
- cancer
