Human slug is a repressor that localizes to sites of active transcription

作     者：Hemavathy, K Guru, SC Harris, J Chen, JD Ip, YT 

作者机构：Univ Massachusetts Sch Med Dept Cell Biol Program Mol Med Worcester MA 01605 USA Univ Massachusetts Sch Med Dept Biochem & Mol Biol Worcester MA 01605 USA Univ Massachusetts Sch Med Dept Mol Pharmacol & Toxicol Worcester MA 01605 USA Natl Human Genome Res Inst Genet & Mol Biol Branch NIH Bethesda MD 20892 USA 

出 版 物：《MOLECULAR AND CELLULAR BIOLOGY》 (分子生物学与细胞生物学)

年 卷 期：2000年第20卷第14期

页      面：5087-5095页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NIDDK NIH HHS [R01 DK052542  R01DK52542] Funding Source: Medline 

主　　题：碱基序列 结合部位 细胞核/遗传学 细胞核/代谢 染色质/代谢 保守序列 DNA结合蛋白质类/代谢 酶抑制剂/药理学 荧光抗体技术 组蛋白脱乙酰基酶抑制剂 组蛋白脱乙酰基酶类/代谢 羟肟酸类/药理学 分子序列数据 肿瘤蛋白质类/免疫学 肿瘤蛋白质类/代谢 核蛋白质类 RNA剪接 阻遏蛋白质类/遗传学 阻遏蛋白质类/免疫学 阻遏蛋白质类/代谢 序列缺失 转录因子/遗传学 转录因子/免疫学 转录因子/代谢 转录 遗传 肿瘤抑制蛋白质类 锌指 人类 

摘      要：Snail/Slug family proteins have been identified in diverse species of both vertebrates and invertebrates. The proteins contain four to six zinc fingers and function as DNA-binding transcriptional regulators. Various members of the family have been demonstrated to regulate cell movement, neural cell fate, left-right asymmetry, cell cycle, and apoptosis. However, the molecular mechanisms of how these regulators function and the target genes involved are largely unknown. In this report, we demonstrate that human Slug (hSlug) is a repressor and modulates both activator-dependent and basal transcription. The repression depends on the C-terminal DNA-binding zinc fingers and on a separable repression domain located in the N terminus. This domain may recruit histone deacetylases to modify the chromatin and effect repression. Protein localization study demonstrates that hSlug is present in discrete foci in the nucleus. This subnuclear pattern does not colocalize with the PML foci or the coiled bodies. Instead, the hSlug foci overlap extensively with areas of the SC-35 staining, some of which have been suggested to be sites of active splicing or transcription. These results lead us to postulate that hSlug localizes to target promoters, where activation occurs, to repress basal and activator-mediated transcription.