The chromatin remodeling factor CSB recruits histone acetyltransferase PCAF to rRNA gene promoters in active state for transcription initiation.

The chromatin remodeling factor CSB recruits histone acetyltransferase PCAF to rRNA gene promoters in active state for transcription initiation.
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染色质重塑因子 CSB 将组蛋白乙酰转移酶 PCAF 募集到活性状态的 rRNA 基因启动子处以启动转录

DOI:
10.1371/journal.pone.0062668
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Tao W
Tao W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shen M;Zhou T;Xie W;Ling T;Zhu Q;Zong L;Lyu G;Gao Q;Zhang F;Tao W

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稳定的rRNA基因的启动子(RDNA)被同色和异染色组蛋白修饰所标记,并与两个转录因子UBF和SL1相关,它们形成转录复合体。活性rRNA基因只含有常染色质的组蛋白修饰,并携带包括RNA聚合酶I在内的转录起始复合体的所有成分,再加上组蛋白乙酰化和RNA聚合酶I靶向,稳定的启动子可以被ATP依赖的染色质重塑因子CSB转化为活性启动子,从而启动rDNA转录。然而,目前还不清楚组蛋白的动态修饰如何诱导聚合酶I转录起始复合体在这种转化过程中组装成活性启动子。在这里,我们发现在rDNA启动子的激活状态下,存在一个由CSB、RNA聚合酶I和组蛋白乙酰转移酶PCAF组成的复合体。CsB是PCAF与rDNA结合所必需的,rDNA可以诱导组蛋白H4和组蛋白H3K9的乙酰化。CSB的过表达促进了PCAF与rDNA的结合。PCAF的敲除导致rDNA启动子H4ac和H3K9ac水平降低,阻止RNA聚合酶I的结合,抑制前-rRNA合成。结果表明,CSB将PCAF招募到rDNA上,使组蛋白乙酰化,这是rRNA基因从稳定状态向活性状态转变过程中聚合酶I转录起始复合体组装所必需的,这表明CSB和PCAF在通过组蛋白乙酰化建立rRNA基因的活性状态方面发挥了协同作用。
The promoters of poised rRNA genes (rDNA) are marked by both euchromatic and heterochromatic histone modifications and are associated with two transcription factors, UBF and SL1 that nucleate transcription complex formation. Active rRNA genes contain only euchromatic histone modifications and are loaded with all components of transcriptional initiation complex including RNA polymerase I. Coupled with histone acetylation and RNA polymerase I targeting, poised promoters can be converted to active ones by ATP-dependent chromatin remodeling factor CSB for initiation of rDNA transcription. However, it is not clear how dynamic histone modifications induce the assembly of polymerase I transcription initiation complex to active promoters during such conversion. Here we show that a complex consisting of CSB, RNA polymerase I and histone acetyltransferase PCAF is present at the rDNA promoters in active state. CSB is required for the association of PCAF with rDNA, which induces acetylation of histone H4 and histone H3K9. Overexpression of CSB promotes the association of PCAF with rDNA. Knockdown of PCAF leads to decreased levels of H4ac and H3K9ac at rDNA promoters, prevents the association of RNA polymerase I and inhibits pre-rRNA synthesis. The results demonstrate that CSB recruits PCAF to rDNA, which allows histone acetylation that is required for the assembly of polymerase I transcription initiation complex during the transition from poised to active state of rRNA genes, suggesting that CSB and PCAF play cooperative roles to establish the active state of rRNA genes by histone acetylation.
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