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基因组H3的CBP/p300介导的乙化在素56上
Chandrima Das1, M Scott Lucia, Kirk C Hansen
1Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA.
Nature
|March 10, 2009
概括
基因组H3 lysine 56 (H3K56ac) 的乙化对于多细胞生物中的DNA修复和复制至关重要. 这项研究确定了参与H3K56ac调节的关键酶和陪伴剂,将其与癌症进展联系起来.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 基因组H3 lysine 56乙化 (H3K56ac) 对于酵母中的DNA复制和修复至关重要.
- 调解H3K56ac的酶是真菌特异的,限制了多细胞真核生物的研究.
研究的目的:
- 研究H3K56ac在多细胞生物中的作用和调节.
- 确定涉及H3K56ac.ac.的甲动物酶和伴侣.
- 探索H3K56ac与癌症之间的联系.
主要方法:
- 酶试验用于识别H3K56.5的组胺乙转移酶 (HAT) 和脱乙酶 (HDAC).
- 在H3K56ac.中分析基因组辅助子参与 (ASF1A,CAF-1)
- 在Drosophila和人类细胞中进行细胞研究,观察DNA损伤和修复期间的H3K56ac动态.
主要成果:
- CBP/Nejire () 和CBP/p300 (人类) 乙酸H3K56;Drosophila Sir2和人类SIRT1/SIRT2脱乙酸H3K56ac.
- 基因组辅导体ASF1A (人) 和Asf1 () 在体内对H3K56的乙化至关重要.
- 为了将H3K56ac纳入染色质中,需要CAF-1 (人类) 和Caf1 (虫).
- 在Drosophila和人类细胞中,H3K56ac在DNA修复部位形成焦点,以应对DNA损伤.
- 在各种癌症中,H3K56ac水平升高,与ASF1A增加相关.
结论:
- H3K56ac在甲基动物中保存,并由特定的HATs,HDACs和基因素辅助体进行调节.
- H3K56ac在DNA损伤部位的染色质组合中起作用.
- 癌症中H3K56ac和ASF1A水平升高表明在瘤发生中可能发挥作用.
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