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RAG2 PHD手指对组合 ヒ斯 H3 氨酸 4 三甲基化与 V(D) J 重组
Adam G W Matthews1, Alex J Kuo, Santiago Ramón-Maiques
1Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature
|November 23, 2007
概括
RAG2蛋白识别了一种特定的组 histone 标记 (H3K4me3),这对 V(D) J 重组至关重要,对免疫系统发育至关重要. 扰乱这种识别会导致免疫缺陷,将组织蛋白修饰与人类遗传性疾病联系起来.
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
- 免疫学 免疫学 免疫学
背景情况:
- 像DNA重组这样的核过程是由染色质结构调节的.
- 质子修饰是已知的转录调节剂,但它们在DNA重组中的作用尚不清楚.
研究的目的:
- 为了研究基因组修饰在哺乳动物DNA重组中的作用.
- 确定V(D) J重组酶的关键组成部分RAG2是否与基因素修饰相互作用.
主要方法:
- 进行X射线晶体学以确定RAG2 PHD指与H3K4me3.3结合的结构.
- 在体内研究以评估影响H3K4me3识别突变对V(D) J重组的影响.
- 对关键残留物突变的患者数据的分析.
主要成果:
- RAG2 包含一个 PHD 指,专门识别在 lysine 4 (H3K4me3) 中三甲基化的 histone H3.
- 晶体结构揭示了这种识别的分子基础.
- 影响H3K4me3识别的突变严重降低了体内V(D) J重组.
- 降低的H3K4me3水平也会降低V(D) J重组.
- 在患有免疫缺陷综合征的患者中发现了一个关键突变 (W453).
结论:
- 希斯甲基化在哺乳动物DNA重组中起着新的作用.
- 通过RAG2破坏基因组修饰识别可以导致遗传性免疫缺陷疾病.
相关概念视频
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Acetylation
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The recognition sites for Cre recombinase called LoxP...
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Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...

