CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter TIP5.
CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter TIP5.
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DOI：
10.1016/j.bbrc.2013.06.045
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发表时间：
2013-07
影响因子：
3.1
通讯作者：
Te Ling;W. Xie;Min Luo;Meili Shen;Qiaoyun Zhu;Le Zong;Tingting Zhou;Jun Gu;Zhigang Lu;Feixiong Zhang;W. Tao
中科院分区：
文献类型：
--
作者：
Te Ling;W. Xie;Min Luo;Meili Shen;Qiaoyun Zhu;Le Zong;Tingting Zhou;Jun Gu;Zhigang Lu;Feixiong Zhang;W. Tao
尽管NuRD（核小体重塑和组蛋白脱乙酰基酶）不能主动地使DNA去甲基化这一公认的事实，但令人惊讶地显示该复合物是在核糖体基因的启动子处建立未甲基化状态所必需的。但是NuRD如何介导rDNA启动子去甲基化的分子机制仍然不清楚。在这里，我们表明，NuRD直接结合到rDNA转录沉默TIP 5（TTF-I相互作用蛋白5）的启动子，核仁重塑复合物NoRC的组成部分之一，沉默rRNA基因通过招募DNA甲基转移酶rDNA启动子和增加DNA甲基化。NuRD负调控TIP 5表达，从而抑制rDNA甲基化并维持rDNA启动子的去甲基化状态。重编程细胞中NuRD组分的缺乏激活TIP 5表达，导致异染色质rRNA基因的比例增加和转录沉默。因此，NuRD能够通过与NoRC复合物的串扰来控制rDNA启动子的甲基化状态。
Despite the well-established fact that NuRD (nucleosome remodeling and histone deacetylase) is incapable of actively demethylating DNA, the complex is surprisingly showed to be required for the establishment of unmethylated state at promoters of ribosomal genes. But the molecular mechanism underlying how NuRD mediates unmethylation at rDNA promoters remains obscure. Here we show that NuRD directly binds to the promoter of rDNA transcription silencer TIP5 (TTF-I interacting protein 5), one of the components of nucleolar remodeling complex NoRC that silences rRNA genes by recruiting DNA methyltransferase to rDNA promoters and increasing DNA methylation. NuRD negatively regulates TIP5 expression, thereby inhibiting rDNA methylation and maintaining demethylation state of rDNA promoters. The deficiency of NuRD components in reprogrammed cells activates TIP5 expression, resulting in the increased fraction of heterochromatic rRNA genes and transcriptional silencing. Thus, NuRD is able to control methylation status of rDNA promoters through crosstalking with NoRC complex.