DNMT1

This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Full Name

DNA Methyltransferase 1

Function

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306).

Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306).

Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306).

Promotes tumor growth (PubMed:24623306).

Biological Process

Cellular response to amino acid stimulus Source: Ensembl
Chromatin organization Source: UniProtKB-KW
DNA methylation Source: ProtInc
DNA methylation involved in embryo development Source: Ensembl
Gene silencing Source: Ensembl
Maintenance of DNA methylation Source: UniProtKB
Negative regulation of gene expression Source: BHF-UCL
Negative regulation of histone H3-K9 methylation Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: ProtInc
Negative regulation of vascular associated smooth muscle cell apoptotic process Source: BHF-UCL
Negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching Source: BHF-UCL
Positive regulation of DNA methylation-dependent heterochromatin assembly Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of histone H3-K4 methylation Source: UniProtKB
Positive regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
Ras protein signal transduction Source: UniProtKB

Cellular Location

Nucleus

Involvement in disease

Neuropathy, hereditary sensory, 1E (HSN1E):
A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN):
An autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy, cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression.

PTM

Sumoylated; sumoylation increases activity.
Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G2/M transition. Deacetylation of Lys-1349 and Lys-1415 by SIRT1 increases methyltransferase activity.
Phosphorylation of Ser-154 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-143 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability.
Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal degradation.
Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.