DNMT1
GeneName
DNMT1
Summary
DNMT1, also known as AIM, Met1, or DNMT, is a 183 kDa DNA methyltransferase that plays a crucial role in maintaining DNA methylation patterns following DNA replication. It is primarily expressed in the nucleus, where it localises to various structures including the nucleoplasm, pericentric heterochromatin, and replication fork. DNMT1 is involved in the regulation of gene expression through its ability to bind to DNA and methylate cytosine residues, thereby influencing chromatin structure and function. Additionally, it has roles in lncRNA binding and promoter-specific chromatin binding, contributing to the epigenetic programming of gene expression.
Importance
DNMT1 is relevant to: - Epigenetic regulation of gene expression, impacting developmental processes and cellular differentiation - Maintenance of genomic stability through its role in DNA methylation, which is vital for proper cell function - Cancer research, as aberrant DNMT1 activity is associated with tumourigenesis and altered gene expression profiles - Vascular biology, given its involvement in the regulation of vascular smooth muscle cell behaviour and differentiation
Top Products
For researchers investigating DNMT1, we recommend two excellent primary antibodies. The first is the well-cited Anti-Dnmt1 antibody [60B1220.1] (ab13537), a trusted choice for Western blotting (WB), immunohistochemistry (IHC), and flow cytometry (FC), with 223 citations highlighting its reliability in the field. Additionally, we offer the recombinant antibody Anti-Dnmt1 antibody [EPR18453] (ab188453), which has been validated in knockout models and is suitable for a broader range of applications, including WB, IHC, immunocytochemistry (ICC), and FC. With 86 citations, this recombinant antibody ensures batch-to-batch consistency, making it an ideal option for researchers seeking dependable DNMT1 detection.
Abcam Product Citation Summary
The data indicates that DNMT1 is a significant target in various studies related to DNA methylation and epigenetic regulation across multiple species, including mouse, rat, and human. The use of Abcam antibodies in Western blotting and ChIP assays highlights the importance of DNMT1 in developmental processes, cancer research, and aging.
Abcam Product Citation Table
Domain
The N-terminal part is required for homodimerization and acts as a regulatory domain.
The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.
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).
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated; sumoylation increases activity.
Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/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 is necessary for the regulation of DNMT1 proteasomal degradation.
Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.
Sequence Similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Tissue Specificity
Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1.
Cellular localization
- Nucleus
- Localized to the perinucleolar region.
Alternative names
AIM, CXXC9, DNMT, DNMT1, DNA (cytosine-5)-methyltransferase 1, Dnmt1, CXXC-type zinc finger protein 9, DNA methyltransferase HsaI, MCMT, DNA MTase HsaI, M.HsaI