SETD8 siRNA – N-Lysine Methyltransferase SETD8 Isoform 1 (Mouse)

SETD8: a protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Methylates K20 of histone H4 (H4K20me1), a specific tag for epigenetic transcriptional repression. SETD8 protein and H4K20me1 levels are cell cycle regulated, both increasing in S phase and peaking at G2/M phase. Interacts with the PCNA protein, associates with sites of active DNA synthesis and is required for DNA replication and genome stability during S phase. Inhibition of SET8 using shRNA results in arrest of replication forks, induction of double-stranded DNA breaks and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Inhibition of SET8 using shRNA results in arrest of replication forks, induction of double-stranded DNA breaks and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle. Nucleosomes are preferred as substrate compared to free histones. Methylates p53K382, leading to repression of the pro-apoptotic and checkpoint activation functions of p53. SET8 expression levels decrease in response to DNA damage, allowing p53 to activate checkpoints and/or apoptosis. Both the methylation of histone H4K20 and p53K382 appear to be important for the functions of SET8 in S phase. Belongs to the histone-lysine methyltransferase family. PR/SET subfamily. Two isoforms of the human protein are produced by alternative splicing.

Protein type: Methyltransferase, protein lysine; Amino Acid Metabolism - lysine degradation; EC 2.1.1.43; Methyltransferase

Cellular Component: nucleolus; chromosome; nucleus

Molecular Function: methyltransferase activity; trimethylamine methyltransferase activity; monomethylamine methyltransferase activity; RNA methyltransferase activity; tRNA (cytosine)-methyltransferase activity; rRNA (cytosine-C5-967)-methyltransferase activity; rRNA (uridine) methyltransferase activity; N-methyltransferase activity; tRNA (guanine) methyltransferase activity; histone-lysine N-methyltransferase activity; rRNA (adenine-N6,N6-)-dimethyltransferase activity; selenocysteine methyltransferase activity; arginine N-methyltransferase activity; protein-arginine N-methyltransferase activity; methanol-specific methylcobalamin:coenzyme M methyltransferase activity; tRNA (guanine-N2-)-methyltransferase activity; dimethylamine methyltransferase activity; protein methyltransferase activity; 2-polyprenyl-6-methoxy-1,4-benzoquinone methyltransferase activity; transferase activity; hydroxyneurosporene-O-methyltransferase activity; rRNA (uridine-2'-O-)-methyltransferase activity; tRNA (uracil) methyltransferase activity; rRNA (adenine) methyltransferase activity; C-methyltransferase activity; transcription corepressor activity; cobalt-precorrin-6B C5-methyltransferase activity; cobalt-precorrin-3 C17-methyltransferase activity; 1-phenanthrol methyltransferase activity; S-methyltransferase activity; lysine N-methyltransferase activity; DNA-methyltransferase activity; tRNA (cytosine-5-)-methyltransferase activity; tRNA (adenine)-methyltransferase activity; C-terminal protein carboxyl methyltransferase activity; rRNA (cytosine) methyltransferase activity; cobalt-precorrin-7 C15-methyltransferase activity; protein-arginine N5-methyltransferase activity; rRNA methyltransferase activity; p53 binding; protein-leucine O-methyltransferase activity; demethylmenaquinone methyltransferase activity; rRNA (adenine-N6-)-methyltransferase activity; tRNA methyltransferase activity; rRNA (guanine) methyltransferase activity; methylarsonite methyltransferase activity; mRNA methyltransferase activity; methylamine-specific methylcobalamin:coenzyme M methyltransferase activity; tRNA (guanine-N1-)-methyltransferase activity; cobalt-precorrin-5B C1-methyltransferase activity; protein-lysine N-methyltransferase activity; O-methyltransferase activity; tRNA (adenine-N1-)-methyltransferase activity; tRNA (adenine-57, 58-N(1)-) methyltransferase activity

Biological Process: methylation; mitosis; transcription, DNA-dependent; regulation of transcription, DNA-dependent; cell division; peptidyl-lysine mono-methylation; chromatin modification; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; cell cycle; regulation of DNA damage response, signal transduction by p53 class mediator