DNMT1 (D63A6) XP? Rabbit mAb

• 产品编号：CST-5032P      品牌：Cell Signaling Technology       原厂货号：5032P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

DNMT1 (D63A6) XP® Rabbit mAb兔单抗能够检测内源性DNMT1总蛋白水平。通过合成的与人源DNMT1蛋白相应的多肽段去免疫动物从而制备出此单克隆抗体。在哺乳动物细胞中DNA在胞嘧啶残基的甲基化是一个可遗传的表观遗传修饰，它对于基因表达、基因组印迹和发育起着关键作用(1,2)。哺乳细胞中DNA甲基转移酶的三个家族已经被鉴定：DNMT1、DNMT2和DNMT3 (1,2)。DNMT1蛋白在增殖的细胞中结构性表达，并且作为维持甲基转移酶的功能，在复制期间可传递合适的甲基到新合成的DNA上。DNMT3A和DNMT3B在胚胎干细胞中高表达，而在成年体细胞组织中表达减少。DNMT3A和DNMT3B蛋白具有在甲基转移酶的初始阶段的功能，该酶能使DNA的未甲基化区域发生甲基化。在成年体细胞组织中DNMT2蛋白在低水平表达，并且它的非活性状态既不影响初始阶段也不影响维持DNA甲基化。DNMT1、DNMT3A和DNMT3B蛋白一起形成一个蛋白复合物，该复合物能与组蛋白去乙酰酶(HDAC1, HDAC2, Sin3A)、转录抑制蛋白(RB, TAZ-1)和异染色质蛋白(HP1, SUV39H1)发生相互作用，从而维持DNA甲基化的合适水平和有助于基因沉默(3-8)。不正确的DNA甲基化导致疾病例如癌症(1,2)。肿瘤抑制基因的启动子CpG岛的高度甲基化与基因沉默和癌症的发展有关。因此，大多数基因组DNA的低甲基化与癌症初始阶段有关并且可能有助于形成。除了结肠、乳腺和胃癌之外，DNMT1、DNMT3A和DNMT3B蛋白在许多癌症中高表达，包括急性和慢性粒细胞性白血病(9-12)。

1. Hermann, A. et al. (2004) Cell. Mol. Life Sci. 61, 2571-2587.
2. Turek-Plewa, J. and Jagodziński, P.P. (2005) Cell. Mol. Biol. Lett. 10, 631-647.
3. Kim, G.D. et al. (2002) EMBO J. 21, 4183-4195.
4. Fuks, F. et al. (2001) EMBO J. 20, 2536-2544.
5. Geiman, T.M. et al. (2004) Biochem. Biophys. Res. Commun. 318, 544-555.
6. Rountree, M.R. et al. (2000) Nat. Genet. 25, 269-277.
7. Pradhan, S. and Kim, G.D. (2002) EMBO J. 21, 779-788.
8. Fuks, F. et al. (2003) Nucleic Acids Res. 31, 2305-2312.
9. Mizuno, S. et al. (2001) Blood 97, 1172-1179.
10. Robertson, K.D. et al. (1999) Nucleic Acids Res. 27, 2291-2298.
11. Xie, S. et al. (1999) Gene 236, 87-95.
12. Kanai, Y. et al. (2001) Int. J. Cancer 91, 205-212.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Hamster, Bovine, Dog, Guinea Pig, Horse

Specificity / Sensitivity

DNMT1 (D63A6) XP® Rabbit mAb detects endogenous levels of total DNMT1 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to the sequence of human DNMT1 protein.

Background

Methylation of DNA at cytosine residues in mammalian cells is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting and development (1,2). Three families of mammalian DNA methyltransferases have been identified: DNMT1, DNMT2 and DNMT3 (1,2). DNMT1 is constitutively expressed in proliferating cells and functions as a maintenance methyltransferase, transferring proper methylation patterns to newly synthesized DNA during replication. DNMT3A and DNMT3B are strongly expressed in embryonic stem cells with reduced expression in adult somatic tissues. DNMT3A and DNMT3B function as de novo methyltransferases that methylate previously unmethylated regions of DNA. DNMT2 is expressed at low levels in adult somatic tissues and its inactivation affects neither de novo nor maintenance DNA methylation. DNMT1, DNMT3A and DNMT3B together form a protein complex that interacts with histone deacetylases (HDAC1, HDAC2, Sin3A), transcriptional repressor proteins (RB, TAZ-1) and heterochromatin proteins (HP1, SUV39H1), to maintain proper levels of DNA methylation and facilitate gene silencing (3-8). Improper DNA methylation contributes to diseased states such as cancer (1,2). Hypermethylation of promoter CpG islands within tumor suppressor genes correlates with gene silencing and the development of cancer. In addition, hypomethylation of bulk genomic DNA correlates with and may contribute to the onset of cancer. DNMT1, DNMT3A and DNMT3B are over-expressed in many cancers, including acute and chronic myelogenous leukemias, in addition to colon, breast and stomach carcinomas (9-12).

1. Hermann, A. et al. (2004) Cell. Mol. Life Sci. 61, 2571-2587.
2. Turek-Plewa, J. and Jagodziński, P.P. (2005) Cell. Mol. Biol. Lett. 10, 631-647.
3. Kim, G.D. et al. (2002) EMBO J. 21, 4183-4195.
4. Fuks, F. et al. (2001) EMBO J. 20, 2536-2544.
5. Geiman, T.M. et al. (2004) Biochem. Biophys. Res. Commun. 318, 544-555.
6. Rountree, M.R. et al. (2000) Nat. Genet. 25, 269-277.
7. Pradhan, S. and Kim, G.D. (2002) EMBO J. 21, 779-788.
8. Fuks, F. et al. (2003) Nucleic Acids Res. 31, 2305-2312.
9. Mizuno, S. et al. (2001) Blood 97, 1172-1179.
10. Robertson, K.D. et al. (1999) Nucleic Acids Res. 27, 2291-2298.
11. Xie, S. et al. (1999) Gene 236, 87-95.
12. Kanai, Y. et al. (2001) Int. J. Cancer 91, 205-212.

注意事项：

Storage: Supplied in 10 mM HEPES (pH 7.5), 150 mM NaCl,
100 µg/ml BSA, 50% glycerol and less than 0.02% sodium
azide. Store at -20°C. Do not aliquot the antibody.