SIN3A (D9D6) Rabbit mAb

• 产品编号：CST-8056S      品牌：CST       原厂货号：8056S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

SIN3A (D9D6) Rabbit mAb兔单抗能够检测内源性SIN3A总蛋白水平。基于蛋白序列，该抗体不能与SIN3B蛋白发生交叉反应。通过人工合成人源SIN3A蛋白Leu530位点周围相应的多肽片段去免疫动物从而制备出此单克隆抗体。SIN3 起初被鉴定在出芽酵母中作为转录的负性调节因子(1,2)。自从那时起，SIN3蛋白的三个亚基在哺乳动物中被鉴定，如同两个不同基因产物一样SIN3A和SIN3B (3,4)。SIN3A和SIN3B都是细胞核蛋白，它们的功能是作为多亚单位SIN3转录抑制复合物的支架亚单位，该复合物包含SIN3A或SIN3B、HDAC1、HDAC2、SDS3、RBBP4/RBAP48、RBBP7/RBAP46、SAP30, and SAP18 (3,4)。SIN3蛋白包含四个paired amphipathic alpha-helix (PAH)结构域，该结构域通过结合大量DNA-结合转录抑制蛋白使SIN3复合物招募到靶基因上 ，而这些转录抑制蛋白包含Mad1、 p53、E2F4、HCF-1、AML1、Elk-1、NRSF、CTCF、ERα和MeCP2 (3,4)。因此，SIN3蛋白包含一个HDAC interaction domain (HID)，该结构域通过SDS3桥接蛋白介导HDAC1和HDAC2的结合，以及在羧基端含有一个highly conserved region (HCR)，该区域有助于抑制性蛋白质结合(3,4)。RBBP4和RBBP7蛋白也结合到SDS3，并且有助于核小体复合物的结合。SIN3复合物的功能去抑制转录，在部分程度上时通过靶基因启动子上的去乙酰化的组蛋白(3,4)。因此，最近研究证明SIN3被招募到抑制性和活性基因的编码区域，在该区域它能使组蛋白去乙酰化以及通过RNA polymerase II抑制假转录(3,5)。除了组蛋白去乙酰化酶活性之外，SIN3复合物与组蛋白甲基化转移酶(ESET)、组蛋白去甲基酶 (JARID1A/RBP2)、ATP依赖的染色质重塑(SWI/SNF)、甲基胞嘧啶双加氧酶(TET1)和O-GlcNAc transferase (OGT) 有关联，这些蛋白都有助于靶基因的调节(5-9)。SIN3复合物对于胚胎发育、细胞生长和增殖、凋亡、DNA复制、DNA修复和DNA甲基化(印记和x染色体失活)起着关键作用(3,4)。

1. Sternberg, P.W. et al. (1987) Cell 48, 567-77.
2. Nasmyth, K. et al. (1987) Cell 48, 579-87.
3. Grzenda, A. et al. Biochim Biophys Acta 1789, 443-50.
4. McDonel, P. et al. (2009) Int J Biochem Cell Biol 41, 108-16.
5. van Oevelen, C. et al. (2008) Mol Cell 32, 359-70.
6. Yang, L. et al. (2003) Biochem J 369, 651-7.
7. Sif, S. et al. (2001) Genes Dev 15, 603-18.
8. Williams, K. et al. (2011) Nature 473, 343-8.
9. Yang, X. et al. (2002) Cell 110, 69-80.

原厂资料：

Specificity / Sensitivity

SIN3A (D9D6) Rabbit mAb recognizes endogenous levels of total SIN3A protein. Based on protein sequence, this antibody is not predicted to cross-react with SIN3B protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Leu530 of human SIN3A protein.

Background

SIN3 was originally identified as a negative regulator of transcription in budding yeast (1,2). Since then, three isoforms of the SIN3 proteins have been identified in mammalian cells, as products of two different genes, SIN3A and SIN3B (3,4). Both SIN3A and SIN3B are nuclear proteins that function as scaffolding subunits for the multi-subunit SIN3 transcriptional repressor complex, containing SIN3A or SIN3B, HDAC1, HDAC2, SDS3, RBBP4/RBAP48, RBBP7/RBAP46, SAP30, and SAP18 (3,4). SIN3 proteins contain four paired amphipathic alpha-helix (PAH) motifs that function in the recruitment of the SIN3 complex to target genes by binding a multitude of DNA-binding transcriptional repressor proteins, including Mad1, p53, E2F4, HCF-1, AML1, Elk-1, NRSF, CTCF, ERα, and MeCP2 (3,4). In addition, SIN3 proteins contain an HDAC interaction domain (HID), which mediates binding of HDAC1 and HDAC2 via the SDS3 bridging protein, and a highly conserved region (HCR) at the carboxy terminus, which contributes to repressor protein binding (3,4). RBBP4 and RBBP7 proteins also bind to SDS3 and contribute to nucleosome binding of the complex. The SIN3 complex functions to repress transcription, in part, by deacetylating histones at target gene promoters (3,4). In addition, recent studies have shown that SIN3 is recruited to the coding regions of repressed and active genes, where it deacetylates histones and suppresses spurious transcription by RNA polymerase II (3,5). In addition to histone deacetylase activity, the SIN3 complex associates with histone methyltransferase (ESET), histone demethylase (JARID1A/RBP2), ATP-dependent chromatin remodeling (SWI/SNF), methylcytosine dioxygenase (TET1), and O-GlcNAc transferase (OGT) activities, all of which appear to contribute to the regulation of target genes (5-9). The SIN3 complex is critical for proper regulation of embryonic development, cell growth and proliferation, apoptosis, DNA replication, DNA repair, and DNA methylation (imprinting and X-chromosome inactivation) (3,4).

1. Sternberg, P.W. et al. (1987) Cell 48, 567-77.
2. Nasmyth, K. et al. (1987) Cell 48, 579-87.
3. Grzenda, A. et al. Biochim Biophys Acta 1789, 443-50.
4. McDonel, P. et al. (2009) Int J Biochem Cell Biol 41, 108-16.
5. van Oevelen, C. et al. (2008) Mol Cell 32, 359-70.
6. Yang, L. et al. (2003) Biochem J 369, 651-7.
7. Sif, S. et al. (2001) Genes Dev 15, 603-18.
8. Williams, K. et al. (2011) Nature 473, 343-8.
9. Yang, X. et al. (2002) Cell 110, 69-80.

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