5月8日，美国科学院院刊（PNAS）在线发表了北京大学生命科学学院陶伟课题组和德国国家癌症研究所Ingrid Grummt教授合作的在表观遗传研究方面的成果。
细胞需要持续不断的核糖体合成来保证蛋白质的合成。核糖体RNA是由RNA聚合酶I来转录的，核糖体基因的转录水平主要由表观遗传机制来控制。这一机制能够高效快速地应答细胞分化、癌化、衰老等信号，来调整核糖体基因的表观遗传修饰状态，从而调控核糖体基因的表达和蛋白质合成水平，最终帮助完成细胞的各种生命活动。
生命科学学院陶伟课题组的研究发现，在核糖体基因启动子区，除转录活跃和转录抑制两种状态的启动子外，还存在另外一类介于转录活跃和转录抑制中间状态的启动子，其核小体处于转录关闭的位置，但却是去甲基化的。同时，伴随着活跃和抑制性的组蛋白修饰，这类启动子上装配有转录起始复合体的前体，可被其它染色质改构复合体进一步调控到活跃转录的表观遗传修饰状态，最终导致转录起始复合体的组装完成和转录起始。
细胞分化过程中核糖体基因的转录抑制，是由于这类启动子不能够被转换成转录活跃的启动子，导致核糖体基因的转录抑制。这些研究表明核糖体基因启动子区域动态的表观遗传修饰调控，可调控转录起始复合体的组装和解聚循环。在应答细胞分化等细胞生命活动时，该动态过程被阻断在中间阶段，使得核糖体基因快速关闭。这种兼具活跃和抑制性的表观遗传修饰，也能够使核糖体基因在细胞活动需要时被快速激活。（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
