|Other Names||DNA (cytosine-5)-methyltransferase 1, Dnmt1, Met-1, DNA methyltransferase MmuI, DNA MTase MmuI, MMmuI, MCMT, Dnmt1, Dnmt, Met1, Uim|
|Target/Specificity||The synthetic peptide sequence used to generate the antibody AP3516a was selected from the region of human Phospho-Dnmt1-pY405. A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.|
|Format||Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Synonyms||Dnmt, Met1, Uim|
|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 (By similarity). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity). Promotes tumor growth (By similarity).|
|Cellular Location||Nucleus. Cytoplasm. Note=It is nucleoplasmic through most of the cell cycle and associates with replication foci during S-phase. In germ cells, spermatogonia, preleptotene and leptotene spermatocytes all express high levels of nuclear protein, while the protein is not detected in pachytene spermatocytes, despite the fact they expressed high levels of mRNA. In females, the protein is not detected in non-growing oocytes, in contrast to the growing oocytes. During the growing, the protein is no longer detectable in nuclei but accumulates to very high levels first throughout the cytoplasm. At the time of ovulation, all the protein is cytoplasmic and is actively associated with the oocyte cortex. After fecondation, in the preimplantation embryo, the protein remains cytoplasmic and after implantation, it is exclusively nuclear in all tissue types Isoform 2 is sequestered in the cytoplasm of maturing oocytes and of preimplantation embryos, except for the 8-cell stage, while isoform 1 is exclusively nuclear|
|Tissue Location||Isoform 1 is expressed in embryonic stem cells and in somatic tissues. Isoform 2 is expressed in oocytes, preimplantation embryos, testis and in skeletal muscle during myogenesis|
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Methylation of DNA at cytosine residues plays an important role in regulation of gene expression, genomic imprinting and is essential for mammalian development. Hypermethylation of CpG islands in tumor suppressor genes or hypomethylation of bulk genomic DNA may be linked with development of cancer. To date, 3 families of mammalian DNA methyltransferase genes have been identified which include Dnmt1, Dnmt2 and Dnmt3. Dnmt1 is constitutively expressed in proliferating cells and inactivation of the Dnmt1 gene causes global demethylation of genomic DNA and embryonic lethality. Dnmt2 is expressed at low levels in adult tissues and its inactivation does not affect DNA methylation or maintenance of methylation. The Dnmt3 family members, Dnmt3a and Dnmt3b, are strongly expressed in ES cells but their expression is down regulated in differentiating ES cells and is low in adult somatic tissue. Dnmt1 co-purifies with the retinoblastoma (Rb) tumour suppressor gene product, E2F1, and HDAC1. Dnmt1 also cooperates with Rb to repress transcription from promoters containing E2Fbinding sites suggesting a link between DNA methylation, histone deacetylase and sequence-specific DNA binding activity, as well as a growth-regulatory pathway that is disrupted in nearly all cancer cells.
Dion,V., Hum. Mol. Genet. 17 (9), 1306-1317 (2008)Yang,L., Genetics 178 (1), 35-45 (2008)
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