WDR5 (D3X5B) Rabbit mAb

• 产品编号：CST-13073S      品牌：CST       原厂货号：13073S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

WDR5 (D3X5B) Rabbit mAb兔单抗能够检测内源性WDR5总蛋白水平。该单克隆抗体是采用合成的与人源WDR5蛋白Pro30残基周围序列相对应的肽段免疫动物而生产的。Set1组蛋白甲基转移酶蛋白首次在酵母中被确认，作为Set1/COMPASS组蛋白甲基转移酶复合物的一部分，该复合物能够使组蛋白H3 Lys4位点发生甲基化，是一种转录共激活因子（1）。 但酵母中只含有一个已知Set1蛋白，哺乳动物中含有六种Set1相关蛋白：SET1A, SET1B, MLL1, MLL2, MLL3,以及MLL4。所有这些都会被组装到COMPASS样复合物中并将组蛋白 H3 Lys4位点甲基化（2,3）。这些Set1相关蛋白的每一个都是在截然不同的蛋白复合物中被发现的，但他们都有共同的亚单位WDR5, RBBP5, ASH2L, CXXC1 以及 DPY30，这些亚单位是复合物正确组装以及组蛋白甲基转移酶活性调节所必需的（2-6）。MLL1和MLL2复合物含有另外一个蛋白亚单位，menin（6）。 像酵母中的Set1一样，所有这六种Set1相关哺乳动物蛋白能够甲基化组蛋白H3的Lys4位点（2-6）。在许多恶性血液病中会发现MLL的易位，这可能暗示着Set1/COMPASS 组蛋白甲基转移酶复合物在白血病发生中具有决定性作用（6）。WDR5是所有SET1/MLL 组蛋白甲基转移酶复合物中的一个核心亚单位，对于复合物的正确组装以及发挥组蛋白甲基转移酶活性是必需（7）。它可以通过招募SET1/MLL复合物至目的基因座并将组蛋白H3用于甲基化的氨基末端尾巴呈现出来，从而作为组蛋白H3 Lys4 甲基化的影响因子来发挥功能（8）。WDR5含有一个典型的七叶片螺旋桨WD40结构域，其中有一个中心凹陷能够在精氨酸甲基转移酶PRMT5 和PRMT7是组蛋白发生对称双甲基化(H3Arg2Me2-S)时与组蛋白H3 的Arg2位点结合当(8)。WDR5与 H3Arg2Me2-S结合后能够导致基因启动子以及远端调控位点上SET1/MLL复合物募集水平以及组蛋白H3Lys4 位点甲基化水平的升高。相反，PRMT6作用下组蛋白H3 Arg2 (H3Arg2Me2-A)发生的非对称双甲基化会降低WDR5的结合并降低SET1/MLL复合物募集水平以及组蛋白H3 Lys4位点甲基化水平（8）。有趣的是，WDR5上的H3Arg2Me2-S结合口袋同样能够与SET1/MLL蛋白的SET结构域以相当的亲和力产生相互作用，从而产生了一种潜在的WDR5的竞争结合，可能用于调控SET1/MLL的募集和随后的H3 Lys4 位点甲基化（9-11）。WDR5还是ATAC和MOF-NSL组蛋白乙酰转移酶复合物以及CHD8 染色质-重构复合物的一个核心亚单位（12-14）。

1. Miller, T. et al. (2001) Proc Natl Acad Sci USA 98, 12902-7.
2. Shilatifard, A. (2008) Curr Opin Cell Biol 20, 341-8.
3. Tenney, K. and Shilatifard, A. (2005) J Cell Biochem 95, 429-36.
4. Lee, J.H. and Skalnik, D.G. (2005) J Biol Chem 280, 41725-31.
5. Lee, J.H. et al. (2007) J Biol Chem 282, 13419-28.
6. Hughes, C.M. et al. (2004) Mol Cell 13, 587-97.
7. Migliori, V. et al. (2012) Epigenetics 7, 815-22.
8. Migliori, V. et al. (2012) Nat Struct Mol Biol 19, 136-44.
9. Song, J.J. and Kingston, R.E. (2008) J Biol Chem 283, 35258-64.
10. Patel, A. et al. (2008) J Biol Chem 283, 32162-75.
11. Zhang, P. et al. (2012) Nucleic Acids Res 40, 4237-46.
12. Wang, Y.L. et al. (2008) J Biol Chem 283, 33808-15.
13. Cai, Y. et al. (2010) J Biol Chem 285, 4268-72.
14. Thompson, B.A. et al. (2008) Mol Cell Biol 28, 3894-904.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Bovine

Specificity / Sensitivity

WDR5 (D3X5B) Rabbit mAb recognizes endogenous levels of total WDR5 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro30 of human WDR5 protein.

Background

The Set1 histone methyltransferase protein was first identified in yeast as part of the Set1/COMPASS histone methyltransferase complex, which methylates histone H3 at Lys4 and functions as a transcriptional co-activator (1). While yeast contain only one known Set1 protein, mammals contain six Set1-related proteins: SET1A, SET1B, MLL1, MLL2, MLL3, and MLL4, all of which assemble into COMPASS-like complexes and methylate histone H3 at Lys4 (2,3). These Set1-related proteins are each found in distinct protein complexes, all of which share the common subunits WDR5, RBBP5, ASH2L, CXXC1 and DPY30, which are required for proper complex assembly and modulation of histone methyltransferase activity (2-6). MLL1 and MLL2 complexes contain the additional protein subunit, menin (6). Like yeast Set1, all six Set1-related mammalian proteins methylate histone H3 at Lys4 (2-6). MLL translocations are found in a large number of hematological malignancies, suggesting that Set1/COMPASS histone methyltransferase complexes play a critical role in leukemogenesis (6).WDR5 is a core subunit of all SET1/MLL histone methyltransferase complexes and is required for proper complex assembly and histone methyltransferase activity (7). It functions as an effector of histone H3 Lys4 methylation by recruiting SET1/MLL complexes to target loci and presenting the histone H3 amino-terminal tail for methylation (8). WDR5 contains a classical, seven-bladed WD40 propeller domain with a central cavity that binds to histone H3 Arg2 when symmetrically di-methylated (H3Arg2Me2-S) by arginine methyltransferases PRMT5 and PRMT7 (8). WDR5 binding to H3Arg2Me2-S results in increased recruitment of SET1/MLL complexes and methylation of histone H3 Lys4 at gene promoters and distal regulatory sites. In contrast, asymmetric di-methylation of histone H3 Arg2 (H3Arg2Me2-A) by PRMT6 reduces WDR5 binding and results in decreased recruitment of SET1/MLL complexes and reduced histone H3 Lys4 methylation (8). Interestingly, the H3Arg2Me2-S binding pocket of WDR5 also interacts with the SET domains of SET1/MLL proteins with comparable affinity, setting up a potential competition for WDR5 binding that may act to regulate SET1/MLL recruitment and subsequent H3 Lys4 methylation (9-11). WDR5 is also a core subunit of the ATAC and MOF-NSL histone acetyltransferase complexes and the CHD8 chromatin-remodeling complex (12-14).

1. Miller, T. et al. (2001) Proc Natl Acad Sci USA 98, 12902-7.
2. Shilatifard, A. (2008) Curr Opin Cell Biol 20, 341-8.
3. Tenney, K. and Shilatifard, A. (2005) J Cell Biochem 95, 429-36.
4. Lee, J.H. and Skalnik, D.G. (2005) J Biol Chem 280, 41725-31.
5. Lee, J.H. et al. (2007) J Biol Chem 282, 13419-28.
6. Hughes, C.M. et al. (2004) Mol Cell 13, 587-97.
7. Migliori, V. et al. (2012) Epigenetics 7, 815-22.
8. Migliori, V. et al. (2012) Nat Struct Mol Biol 19, 136-44.
9. Song, J.J. and Kingston, R.E. (2008) J Biol Chem 283, 35258-64.
10. Patel, A. et al. (2008) J Biol Chem 283, 32162-75.
11. Zhang, P. et al. (2012) Nucleic Acids Res 40, 4237-46.
12. Wang, Y.L. et al. (2008) J Biol Chem 283, 33808-15.
13. Cai, Y. et al. (2010) J Biol Chem 285, 4268-72.
14. Thompson, B.A. et al. (2008) Mol Cell Biol 28, 3894-904.

注意事项：

Storage: Supplied in 10 mM sodium 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