SUV39H1

SUV39H1 (suppressor of variegation 3~9 homolog 1) is the first histone lysine methyltransferase to be found, mainly involved in H3K9 trimethylation (H3K9m3). The currently known H3K9 methyltransferases include SU(VAR) 3-9 in Drosophila, Clr4 in Schizosaccharomyces, Suv39h1, Suv39h2, G9a, G9a-related proteins (GLP) and SETDB1/ESET in mammals, among which G9a and SUV39H1 are important enzymes for histone H3K9 methylation. Human SUV39H1 is composed of 412 amino acids and has a SET domain, which is involved in the formation of heterochromatin. G9a is the main chromatin H3K9 methyltransferase, which catalyzes the monomethylation and dimethylation of H3K9 in the euchromatin region. H3K9 methylation is important for the formation of heterochromatin in most eukaryotic cells. The H3K9 methyltransferase SUV39 family is thought to be a major determinant of heterochromatin formation. Heterochromatin regulates cell division and proliferation in the cell cycle and plays an important role in gene regulation. The proteins that can bind to methylated H3K9 are mainly heterochromatin binding protein 1 (HP1) and UHRF1 (ubiquitin-like, containing PHD, RING finger domains 1). In human cells, HP1 regulates gene transcription and participates in the formation of heterochromatin, which is the key to maintaining chromatin structure and ensuring smooth cell mitosis. The SUV39H1 protein acts as an H3K9-specific methyltransferase that interacts with certain DNA-binding proteins to promote target gene silencing and mediate leukemia. RUNX1 is one of the most common targets for chromosomal translocation of leukemia. SUV39H1 binds to the transcriptional repressor domain RD2 of RUNX1 and plays a role in transcriptional repression and gene silencing. In acute promyelocytic leukemia, the fusion protein encoded by the PML-RARa fusion gene on chromosome 15 and chromosome 17 has gene transcriptional inhibition. The study found that PML-RAR can recruit SUV39H1 to the target gene promoter region to form PML-RAR/SUV39H1 complex, catalyze H3K9 methylation, inhibit gene transcription, and hinder the development of blood cell differentiation. In some patients with acute leukemia and MDS, the EVI1 gene is overexpressed, and the zinc finger protein encoded by it can specifically bind to the DNA sequence of the gene promoter and play a transcriptional regulatory role. Cattaneo et al. found that SUV39H1 binds to EVI1 to form an EVI1/SUV39H1 complex with high histone methyltransferase activity, which inhibits gene transcription. The knockdown of SUV39H1 or G9a gene by RNAi technology can significantly inhibit the proliferation of cancer cell clones, suggesting that in EVI1-positive leukemia patients, histone methyltransferase site is expected to be a therapeutic target and improve disease prognosis.