5月8日，美國科學院院刊（PNAS）在線發(fā)表了北京大學生命科學學院陶偉課題組和德國國家癌癥研究所Ingrid Grummt教授合作的在表觀遺傳研究方面的成果,。
細胞需要持續(xù)不斷的核糖體合成來保證蛋白質(zhì)的合成。核糖體RNA是由RNA聚合酶I來轉(zhuǎn)錄的,，核糖體基因的轉(zhuǎn)錄水平主要由表觀遺傳機制來控制,。這一機制能夠高效快速地應(yīng)答細胞分化、癌化,、衰老等信號,，來調(diào)整核糖體基因的表觀遺傳修飾狀態(tài)，從而調(diào)控核糖體基因的表達和蛋白質(zhì)合成水平,，最終幫助完成細胞的各種生命活動,。
生命科學學院陶偉課題組的研究發(fā)現(xiàn)，在核糖體基因啟動子區(qū),，除轉(zhuǎn)錄活躍和轉(zhuǎn)錄抑制兩種狀態(tài)的啟動子外,，還存在另外一類介于轉(zhuǎn)錄活躍和轉(zhuǎn)錄抑制中間狀態(tài)的啟動子，其核小體處于轉(zhuǎn)錄關(guān)閉的位置,，但卻是去甲基化的,。同時，伴隨著活躍和抑制性的組蛋白修飾,，這類啟動子上裝配有轉(zhuǎn)錄起始復合體的前體,，可被其它染色質(zhì)改構(gòu)復合體進一步調(diào)控到活躍轉(zhuǎn)錄的表觀遺傳修飾狀態(tài)，最終導致轉(zhuǎn)錄起始復合體的組裝完成和轉(zhuǎn)錄起始,。
細胞分化過程中核糖體基因的轉(zhuǎn)錄抑制,，是由于這類啟動子不能夠被轉(zhuǎn)換成轉(zhuǎn)錄活躍的啟動子，導致核糖體基因的轉(zhuǎn)錄抑制,。這些研究表明核糖體基因啟動子區(qū)域動態(tài)的表觀遺傳修飾調(diào)控,，可調(diào)控轉(zhuǎn)錄起始復合體的組裝和解聚循環(huán)。在應(yīng)答細胞分化等細胞生命活動時,，該動態(tài)過程被阻斷在中間階段,，使得核糖體基因快速關(guān)閉。這種兼具活躍和抑制性的表觀遺傳修飾,，也能夠使核糖體基因在細胞活動需要時被快速激活,。（生物谷Bioon.com）
doi:10.1073/pnas.1201262109
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The chromatin remodeling complex NuRD establishes the poised state of rRNA genes characterized by bivalent histone modifications and altered nucleosome positions
Wenbing Xiea,1, Te Linga,1, Yonggang Zhoub,1,2, Weijun Fengb, Qiaoyun Zhua, Henk G. Stunnenbergc, Ingrid Grummtb,3, and Wei Taoa,3
rRNA genes (rDNA) exist in two distinct epigenetic states, active promoters being unmethylated and marked by euchromatic histone modifications, whereas silent ones are methylated and exhibit heterochromatic features. Here we show that the nucleosome remodeling and deacetylation (NuRD) complex establishes a specific chromatin structure at rRNA genes that are poised for transcription activation. The promoter of poised rRNA genes is unmethylated, associated with components of the preinitiation complex, marked by bivalent histone modifications and covered by a nucleosome in the “off” position, which is refractory to transcription initiation. Repression of rDNA transcription in growth-arrested and differentiated cells correlates with elevated association of NuRD and increased levels of poised rRNA genes. Reactivation of transcription requires resetting the promoter-bound nucleosome into the “on” position by the DNA-dependent ATPase CSB (Cockayne syndrome protein B). The results uncover a unique mechanism by which ATP-dependent chromatin remodeling complexes with opposing activities establish a specific chromatin state and regulate transcription
