组蛋白H3K4去甲基化酶AOF1及其酶活性非依赖的转录抑制功能

发布时间：2018-04-26 15:01

本文选题：AOF1 + 组蛋白　；参考：《华东师范大学》2010年硕士论文

【摘要】： LSD1依据新的命名法为KDM1)作为第一个鉴定的组蛋白去甲基化酶,主要特异的作用于赖氨酸,属于四羟酮醇依赖型氨基酸氧化酶家族。我们在这里所报道的AOF1(依据新的命名法为KDM1B),是哺乳动物体内同LSD1相似的蛋白,其同样具有组蛋白H3K4mel and H3K4me2位点特异的去甲基化酶活性。和LSD1相似的是,其高度保守的SWIRM结构域是其酶活性所必需的。然而AOF1存在着与LSD1质不同的几个方面。首先,AOF1不与组蛋白去乙酰化酶共同形成稳定的复合体；其次,AOF1在细胞周期中的分裂期定位于染色体上,而LSD1并不存在同样的定位关系；此外,当AOF1与DNA结合时可以抑制转录,而这种转录抑制的功能是独立于其去甲基化酶活性的。通过结构和功能的分析,我们鉴定出AOF1的氮末端的Zf-CW结构域是其转录抑制功能所必需的。总的来讲：我们的研究鉴定了AOF1作为四羟酮醇依赖型氨基酸氧化酶家族第二个组蛋白去甲基化酶,并且揭示了其去甲基化酶活性非依赖的转录抑制功能。
[Abstract]:LSD1 is the first histone demethylase identified by a new method named KDM1. It mainly acts specifically on lysine and belongs to the family of tetrahydroxy keto-dependent amino acid oxidase. We report here that AOF1 (KDM1BN) is a protein similar to LSD1 in mammals, which also has histone H3K4mel and H3K4me2 site-specific demethylase activity. Similar to LSD1, its highly conserved SWIRM domain is necessary for its enzyme activity. However, there are several aspects of AOF1 that are different from those of LSD1. First, AOF1 does not form a stable complex with histone deacetylase; second, AOF1 is located on chromosomes in the mitotic phase of cell cycle, but LSD1 does not have the same localization relationship. In addition, when AOF1 binds to DNA, it inhibits transcription. The function of this transcriptional inhibition is independent of its demethylase activity. By structural and functional analysis, we identified the Zf-CW domain at the nitrogen end of AOF1 as essential for its transcriptional inhibition. In general, our studies have identified AOF1 as the second histone demethylase of the tetrahydroxy keto-dependent amino acid oxidase family, and revealed its non-dependent transcriptional inhibitory function.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R341

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