我們機體細胞中的遺傳物質(zhì)包括活躍和非活躍區(qū)域,,當活躍區(qū)域的基因被閱讀以后,,非活躍的區(qū)域依然保持著封鎖狀態(tài),?;蚪M中這些功能性的保守性,、緊密的區(qū)域?qū)τ诨蛘{(diào)節(jié)以及細胞分裂期間染色體的穩(wěn)定性和正確分散至關(guān)重要,。這些結(jié)構(gòu)區(qū)域可以被遺傳物質(zhì)或者組蛋白類進行生化特異性地修飾。在果蠅中識別出的異染色質(zhì)蛋白質(zhì)1(HP1)可以特異性地結(jié)合修飾過高特異性的組蛋白,,并且保證關(guān)閉區(qū)域的失活,。
HP1可以監(jiān)視遺傳物質(zhì)的失活
HP1可以特異性地集合被標記的組蛋白并且關(guān)閉其基因組序列,,使用一種酵母生物學及生物物理學的結(jié)合技術(shù),研究者從分子水平揭示了這個過程,。HP1可以攔截受抑制的遺傳物質(zhì)的RNA轉(zhuǎn)錄,,并且護送這些分子至細胞機器中,然后降解它們,。同時,,一種新的HP1可以占據(jù)組蛋白中騰出的空間。這種連續(xù)性的逆轉(zhuǎn)保證了來自失活區(qū)域的RNA轉(zhuǎn)錄是持續(xù)被破壞的,。
動態(tài)交互作用
生物物理學的方法揭示了HP1可以動態(tài)操控染色質(zhì)的狀態(tài),。這種動力循環(huán)允許細胞在同一時間、不同水平上來控制基因的鈍化,。研究者的發(fā)現(xiàn)闡述了在酵母中HP1的重要性,。然而,HP1一直在進化之中,,而且目前只存在于人類細胞中,,未來演技組合希望通過揭示其在男性中所扮演的角色,并且進一步研究HP1的結(jié)構(gòu),。相關(guān)研究成果刊登在了近日的國際雜志Molecular Cell上,。(生物谷Bioon.com)
編譯自:Molecular controller switches off genetic material
編譯者:T.Shen
doi:10.1016/j.molcel.2012.05.009
PMC:
PMID:
HP1Swi6 Mediates the Recognition and Destruction of Heterochromatic RNA Transcripts
Claudia Keller1, 2, Ricardo Adaixo3, Rieka Stunnenberg1, 2, Katrina J. Woolcock1, 2, Sebastian Hiller3, , , Marc Bühler1, 2, ,
HP1 proteins are major components of heterochromatin, which is generally perceived to be an inert and transcriptionally inactive chromatin structure. Yet, HP1 binding to chromatin is highly dynamic and robust silencing of heterochromatic genes can involve RNA processing. Here, we demonstrate by a combination of in vivo and in vitro experiments that the fission yeast HP1Swi6 protein guarantees tight repression of heterochromatic genes through RNA sequestration and degradation. Stimulated by positively charged residues in the hinge region, RNA competes with methylated histone H3K9 for binding to the chromodomain of HP1Swi6. Hence, HP1Swi6 binding to RNA is incompatible with stable heterochromatin association. We propose a model in which an ensemble of HP1Swi6 proteins functions as a heterochromatin-specific checkpoint, capturing and priming heterochromatic RNAs for the RNA degradation machinery. Sustaining a functional checkpoint requires continuous exchange of HP1Swi6 within heterochromatin, which explains the dynamic localization of HP1 proteins on heterochromatin.