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在Polycomb沉声器中素H2A无处不在的作用
Hengbin Wang1, Liangjun Wang, Hediye Erdjument-Bromage
1Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Nature
|September 24, 2004
概括
研究人员确定了人体Polycomb抑制复合物1-like (hPRC1L) 作为负责基因素H2A无处置的酶. 这一发现将H2A无处不在与Polycomb基因沉默机制联系起来.
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
- 生物化学 生物化学
背景情况:
- 协同基因组修饰调节染色体动力学和基因转录.
- 在这些过程中,基因组无处不在,特别是在H2A和H2B上,起着至关重要的作用.
- 虽然已知H2B无化酶及其与甲基化交叉反应,但H2A无化酶和功能在很大程度上仍未被描述.
研究的目的:
- 为了识别和表征E3无酸酶复合体,负责组素H2A的无酸化.
- 阐明H2A无化在基因调节中的功能性作用.
主要方法:
- 净化和功能性表征的 histone H2A E3 泛素合酶复合体.
- 使用细胞和遗传方法减少关键复杂元件 (例如,Ring2) 的表达.
- 染色体免疫沉 (ChIP) 来评估蛋白质局部化和组织蛋白修饰.
- 通过RNA干扰 (RNAi) 来研究H2A无化损失后的基因减压.
主要成果:
- 鉴定人体Polycomb抑制复合物1-like (hPRC1L) 作为一种特定的E3泛基因酶,用于基因素H2A.
- hPRC1L 在氨酸19.9 的 monoubiquitinates 基因组 H2A.
- 减少Ring2表达导致H2A无处不在水平降低.
- 在 Ubx 基因的调节区域中,dRing (Drosophila 同类物的一个组成部分) 与无处不在的 H2A 的局部化.
- 丢失dRing和H2A无处不在导致Ubx基因脱压.
结论:
- 这项研究确定了特定的E3泛素结合酶复合体 (hPRC1L),该复合体负责组织素H2A泛化.
- 由hPRC1L介导的基因组H2A无处不在,与Polycomb介导的基因沉默功能相关.
- 这项工作为通过基因组修饰对表观遗传调节的机制提供了关键的见解.
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