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組蛋白H3K4去甲基化酶AOF1及其酶活性非依賴的轉(zhuǎn)錄抑制功能

發(fā)布時間:2018-04-26 15:01

  本文選題:AOF1 + 組蛋白; 參考:《華東師范大學》2010年碩士論文


【摘要】: LSD1依據(jù)新的命名法為KDM1)作為第一個鑒定的組蛋白去甲基化酶,主要特異的作用于賴氨酸,屬于四羥酮醇依賴型氨基酸氧化酶家族。我們在這里所報道的AOF1(依據(jù)新的命名法為KDM1B),是哺乳動物體內(nèi)同LSD1相似的蛋白,其同樣具有組蛋白H3K4mel and H3K4me2位點特異的去甲基化酶活性。和LSD1相似的是,其高度保守的SWIRM結(jié)構(gòu)域是其酶活性所必需的。然而AOF1存在著與LSD1質(zhì)不同的幾個方面。首先,AOF1不與組蛋白去乙酰化酶共同形成穩(wěn)定的復(fù)合體;其次,AOF1在細胞周期中的分裂期定位于染色體上,而LSD1并不存在同樣的定位關(guān)系;此外,當AOF1與DNA結(jié)合時可以抑制轉(zhuǎn)錄,而這種轉(zhuǎn)錄抑制的功能是獨立于其去甲基化酶活性的。通過結(jié)構(gòu)和功能的分析,我們鑒定出AOF1的氮末端的Zf-CW結(jié)構(gòu)域是其轉(zhuǎn)錄抑制功能所必需的?偟膩碇v:我們的研究鑒定了AOF1作為四羥酮醇依賴型氨基酸氧化酶家族第二個組蛋白去甲基化酶,并且揭示了其去甲基化酶活性非依賴的轉(zhuǎn)錄抑制功能。
[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.
【學位授予單位】:華東師范大學
【學位級別】:碩士
【學位授予年份】:2010
【分類號】:R341

【參考文獻】

相關(guān)期刊論文 前1條

1 ;Epigenetic regulation: methylation of histone and non-histone proteins[J];Science in China(Series C:Life Sciences);2009年04期

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本文編號:1806517

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