Epigenetics is the process of heritable change in gene activity despite alteration of the hosts DNA sequence, essentially causing a change in a phenotype without a change in the genotype of a host. To change the gene sequence without interfering with the DNA is accomplished by histone and DNA methylation. Gene silencing in DNA methylation is carried out by DNA methyltransferases 1, 2 and 3a/b (DNMT1, DNMT2, DNMT3A/B). On a broad level, DNMT’s methylate the fifth carbon of cytosine residues in DNA within CG dinucleotides. However, DNMT3B is required for genome-wide de novo methylation and is during development. DNMT3B also specifically regulates DNA of nucleosomal DNA, however it can also act as a transcriptional co-repressor by associating with CBX4 in lieu of methylation. Studies on the structure of DNMT3 have revealed that DNMT3A and DNMT3B are highly similar in that they both contain a PWWP domain, a PHD-like ADD domain and a catalytic domain. Mutations in DNMT3B yield developmental diseases, one of which is immunodeficiency-centromeric instability-facial anomalies syndrome.
DNMT3B Antibody (52A1018) [NB100-56514] - Simple Western lane view shows a specific band for Dnmt3b in 0.5 mg/ml of NIH-3T3 lysate. This experiment was performed under reducing conditions using the 12-230 kDa separation system.
The activity of genetic regulation and tumor gene suppression is an interesting combination in a variety of cancers. It is clear that epigenetic abnormalities occur in tumors, and also clear that gene dysregulation occurs during malignant transformation. Palakurthy et al discovered an interesting pathway for the gene silencing of the tumor suppressor RASSF1A using a DNMT3B antibody. They found that RASSF1A is silenced through DNMT3B with HOXB3. Ultimately, they used a DNMT3B antibody to show that DNMT3B is recruited to the RASSF1A promoter, resulting in exaggerated DNA methylation and silencing of RASSF1A expression. This pathway is now being proposed in a variety of cancers.
Joensuu et al did a comprehensive study using DNMT3B antibodies to look at tumor gene suppression and methylation in 165 tumors. Their results concluded that methyltransferase expression and activity is tissue dependent and also relies on specific cellular proliferation properties. Specifically, they used a DNMT3B antibody to find that DNMT3B acts within a distal promoter region. Moreover, they found that there is no real correlation between tumor suppressor gene properties and methyltransferase activity, despite the two processes being present in malignant tumor development. Lastly, Butcher et al used a DNMT3B antibody in the immunohistochemistry application to find that epigenetic inactivation of BRCA1 is associated with DNMT3B in sporadic breast tumors. These findings may help to diagnose other breast tumors by way of revealing epigenetically silenced genes.
Novus Biologicals offers DNMT3B reagents for your research needs including:
- PMID: 26305882
- PMID: 19854132
- PMID: 17071074