UBF levels determine the number of active ribosomal RNA genes in mammals.
UBF levels determine the number of active ribosomal RNA genes in mammals.
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DOI：
10.1083/jcb.200805146
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发表时间：
2008-12-29
期刊：
影响因子：
--
通讯作者：
Hannan RD
中科院分区：
文献类型：
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作者：
Sanij E;Poortinga G;Sharkey K;Hung S;Holloway TP;Quin J;Robb E;Wong LH;Thomas WG;Stefanovsky V;Moss T;Rothblum L;Hannan KM;McArthur GA;Pearson RB;Hannan RD
在哺乳动物中，由RNA聚合酶I转录的10200个核糖体RNA（rRNA）基因的活性拷贝数的调节机制尚不清楚。我们证明，耗尽的转录因子上游结合因子（UBF）导致稳定和可逆的甲基化独立沉默的rRNA基因，通过促进组蛋白H1诱导的组装转录活性染色质。染色质重塑被UBF 1的高迁移率族蛋白1结构域内的细胞外信号调节激酶位点的突变所消除，这是UBF 1在体外弯曲和环化DNA的能力所必需的。令人惊讶的是，rRNA基因沉默不会减少净rRNA合成，因为剩余活性基因的转录增加。我们还表明，活跃的rRNA基因库不是静态的，而是在分化过程中减少，与UBF表达减少相关。因此，UBF 1水平在生长和分化过程中调节活性rRNA基因染色质。
In mammals, the mechanisms regulating the number of active copies of the ∼200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1–induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation.