SUV39H1

This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants.

Full Name

Suppressor Of Variegation 3-9 Homolog 1

Function

Histone methyltransferase that 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 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and 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 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of 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. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.

Biological Process

Biological Process cell cycleIEA:UniProtKB-KW
Biological Process cell differentiationIEA:UniProtKB-KW
Biological Process cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:MGI
Biological Process cellular response to glucose starvationManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process cellular response to hypoxiaManual Assertion Based On ExperimentIDA:MGI
Biological Process chromatin organizationManual Assertion Based On ExperimentTAS:ProtInc
Biological Process energy homeostasisManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process histone H3-K9 dimethylationISS:UniProtKB
Biological Process histone H3-K9 trimethylationISS:UniProtKB
Biological Process histone lysine methylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of cell cycleManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process negative regulation of circadian rhythmISS:UniProtKB
Biological Process negative regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:MGI
Biological Process positive regulation of histone deacetylationManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process positive regulation of histone methylationManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process rDNA heterochromatin assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of transcription by glucoseManual Assertion Based On ExperimentIMP:ComplexPortal
Biological Process rhythmic processIEA:UniProtKB-KW
Biological Process rRNA processingIEA:UniProtKB-KW

Cellular Location

Nucleus
Nucleus lamina
Nucleus, nucleoplasm
Chromosome, centromere
Associates with centromeric constitutive heterochromatin.

PTM

Phosphorylated on serine residues, and to a lesser degree, on threonine residues. The phosphorylated form is stabilized by SBF1 and is less active in its transcriptional repressor function.
Acetylated at Lys-266, leading to inhibition of enzyme activity. SIRT1-mediated deacetylation relieves this inhibition.