Monoclonal Antibody to Dnmt3a (Clone 64B814.1)

Background
Methylation of deoxyribonucleic acids 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, three 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 this 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. Recently, it has been shown that naturally occurring mutations of Dnmt3b gene occurs in patients with a rare autosomal recessive disorder, termed ICF (immunodeficiency, centromeric instability, and facial anomalies) syndrome.

Antigen
This antibody was raised against bacteria expressed recombinant mouse Dnmt3a.

Genebank Info (Protein)
NP_715640

Reference
1. Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E. Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene. 1999 Aug 5;236(1):87-95.
2. Okano M, Bell DW, Haber DA,a nd Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99: 247-257 (1999).
3. Reik W, Kelsey G, and Walter J. Dissecting de novo methylation. Nat. Genet 23: 380-382 (1999).
4. Ling,Y., Sankpal,U.T., Robertson,A.K., McNally,J.G., Karpova,T. and Robertson,K.D. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res. 32 (2), 598-610 (2004).
5. Kaneda,M., Okano,M., Hata,K., Sado,T., Tsujimoto,N., Li,E. and Sasaki,H. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429 (6994), 900-903 (2004).
6. Yoder, J.A., et al. 1997. DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J. Mol. Biol. 270: 385-395.
7. Hsieh, C.L. 1999. In vivo activity of murine de novo methyltransferases, Dnmt3a and Dnmt3b. Mol. Cell Biol. 19: 8211-8218.
8. Fuks,F., Burgers,W.A., Godin,N., Kasai,M. and Kouzarides,T. Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J. 20 (10), 2536-2544 (2001).
9. Gowher,H. and Jeltsch,A. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases J. Biol. Chem. 277 (23), 20409-20414 (2002).
10. Datta,J., Ghoshal,K., Sharma,S.M., Tajima,S. and Jacob,S.T. Biochemical fractionation reveals association of DNA methyltransferase (Dnmt) 3b with Dnmt1 and that of Dnmt 3a with a histone H3 methyltransferase and Hdac1 J. Cell. Biochem. 88 (5), 855-864 (2003).