6月14日,，Cell雜志在線報(bào)道了一種新穎的體內(nèi)測(cè)定染色質(zhì)修飾動(dòng)力學(xué)的方法,。組蛋白翻譯后修飾是非常重要的基因調(diào)控,，但其傳播的模式和對(duì)可遺傳基因表達(dá)狀態(tài)的貢獻(xiàn)大小仍存在爭(zhēng)議。為了解決這些問題,，研究者開發(fā)了一種染色質(zhì)體內(nèi)試驗(yàn)（CiA）系統(tǒng),，采用化學(xué)誘導(dǎo)接近，啟動(dòng)和終止在活細(xì)胞中的染色質(zhì)修飾,。
研究者選擇性招募HP1α來誘導(dǎo)H3K9me3依賴的基因沉默,，并描述成纖維細(xì)胞和多能干細(xì)胞中，Oct4基因位點(diǎn)染色質(zhì)修飾的程度和動(dòng)力學(xué),。 H3K9me3以平均0.18核小體/小時(shí)的速率對(duì)稱性傳播,，由此產(chǎn)生高達(dá)10 KB的區(qū)域。去除HP1α刺激后,，異染色質(zhì)域可遺傳到子代細(xì)胞,，經(jīng)多個(gè)細(xì)胞世代而不消減,。該研究的數(shù)據(jù),，使定量模擬反應(yīng)動(dòng)力學(xué)成為可能。
這表明,，組蛋白標(biāo)記和去除之間的動(dòng)態(tài)競(jìng)爭(zhēng),，決定著H3K9me3域的邊界和穩(wěn)定性。這個(gè)框架可預(yù)測(cè)基因組中大部分常染色質(zhì)H3K9me3域的穩(wěn)態(tài)動(dòng)力學(xué)和空間特點(diǎn),。
這一研究成果,，大大提高了人類對(duì)通過組蛋白翻譯后修飾調(diào)控基因表達(dá)生物過程的認(rèn)識(shí)。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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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.
