A Cul4 E3 泛素酶调节核细胞组组合期间的质子移交过程
Junhong Han1, Hui Zhang, Honglian Zhang
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Cell
|November 12, 2013
概括
基因组辅导体Asf1与新合成的H3-H4.4结合在一起. 保守的E3酶向乙化H3进行无处不在,促进H3-H4转移和核细胞组合. 这揭示了基因素乙化和无处不在化之间的交叉声.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 染色体生物学 染色体生物学
背景情况:
- 核细胞组合对基因组稳定性和DNA复制和转录后的表观遗传至关重要.
- 包括Asf1在内的基因组辅导体,管理新合成的基因组H3-H4.4.
- 由于Asf1的高亲和力,从Asf1转移H3-H4到其他伴侣的机制仍然不清楚.
研究的目的:
- 为了研究调节H3-H4从Asf1伴侣复合体转移的机制.
- 为了确定介导核细胞组装H3-H4释放的因素.
- 在这个过程中探索基因素乙化和无处不在化之间的相互作用.
主要方法:
- 使用酵母模型研究Rtt101 (((Mms1) E3泛基因酶.
- 研究了基因素H3的结合和无处不在,特别是在lysine56处乙化.
- 采用了Rtt101和H3.3的基因失活和局部定向突变发生.
- 检查了核细胞组合效率和Asf1-H3相互作用.
- 在使用Cul4A(DDB1) 枯竭的人类细胞中得到证实.
主要成果:
- 酵母Rtt101 (((Mms1) E3泛素结合酶特别结合和泛化新合成的基H3在氨酸56中被乙化.
- 在H3上Rtt101的失活或无处不在位点的突变会损害核细胞组合.
- 这些遗传变化还增强了Asf1和H3之间的相互作用.
- 在缺乏Cul4A的人类细胞中观察到类似的核细胞组装缺陷和改变的伴侣相互作用.
结论:
- 一个保存的E3连接酶 (Rtt101(Mms1) /Cul4A(DDB1)) 调节了从Asf1伴侣复合体中H3-H4的转移.
- 基因组H3的无处不在,特别是在K56中,是促进这种转移的关键步骤.
- 在核细胞组合和表观遗传维护的调节中,证明了基因素乙化和无处不在化之间的交叉声.
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