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Cell:测定活细胞内异染色质动力学的新方法

来源:生物谷 2012-06-19 15:12


6月14日,Cell杂志在线报道了一种新颖的体内测定染色质修饰动力学的方法。组蛋白翻译后修饰是非常重要的基因调控,但其传播的模式和对可遗传基因表达状态的贡献大小仍存在争议。为了解决这些问题,研究者开发了一种染色质体内试验(CiA)系统,采用化学诱导接近,启动和终止在活细胞中的染色质修饰。

研究者选择性招募HP1α来诱导H3K9me3依赖的基因沉默,并描述成纤维细胞和多能干细胞中,Oct4基因位点染色质修饰的程度和动力学。 H3K9me3以平均0.18核小体/小时的速率对称性传播,由此产生高达10 KB的区域。去除HP1α刺激后,异染色质域可遗传到子代细胞,经多个细胞世代而不消减。该研究的数据,使定量模拟反应动力学成为可能。

这表明,组蛋白标记和去除之间的动态竞争,决定着H3K9me3域的边界和稳定性。这个框架可预测基因组中大部分常染色质H3K9me3域的稳态动力学和空间特点。

这一研究成果,大大提高了人类对通过组蛋白翻译后修饰调控基因表达生物过程的认识。(生物谷bioon.com)

 

Dynamics and Memory of Heterochromatin in Living Cells

Nathaniel A. Hathaway, Oliver Bell, Courtney Hodges, Erik L. Miller, Dana S. Neel, Gerald R. Crabtree

Posttranslational histone modifications are important for gene regulation, yet the mode of propagation and the contribution to heritable gene expression states remains controversial. To address these questions, we developed a chromatin in vivo assay (CiA) system employing chemically induced proximity to initiate and terminate chromatin modifications in living cells. We selectively recruited HP1α to induce H3K9me3-dependent gene silencing and describe the kinetics and extent of chromatin modifications at the Oct4 locus in fibroblasts and pluripotent cells. H3K9me3 propagated symmetrically and continuously at average rates of 0.18 nucleosomes/hr to produce domains of up to 10 kb. After removal of the HP1α stimulus, heterochromatic domains were heritably transmitted, undiminished through multiple cell generations. Our data enabled quantitative modeling of reaction kinetics, which revealed that dynamic competition between histone marking and turnover, determines the boundaries and stability of H3K9me3 domains. This framework predicts the steady-state dynamics and spatial features of the majority of euchromatic H3K9me3 domains over the genome.

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