Integrative genomic analysis of human ribosomal DNA.

Integrative genomic analysis of human ribosomal DNA.
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DOI:
10.1093/nar/gkq1326
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发表时间:
2011-07
影响因子:
14.9
通讯作者:
Scacheri PC
Scacheri PC
中科院分区:
生物学2区
文献类型:
--
作者:
Zentner GE;Saiakhova A;Manaenkov P;Adams MD;Scacheri PC

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核糖体 RNA (rRNA) 的转录对生命至关重要。尽管核糖体 DNA (rDNA) 很重要,但它并不包含在当前的基因组组装中,因此迄今为止的基因组分析已将 rDNA 排除在外。在这里,我们展示了短序列读取可以与包含单个 rDNA 重复的基因组组装进行比对。 ChIP-seq、DNase-seq、MNase-seq 和 RNA-seq 数据的综合分析揭示了一些新发现。首先,活性 rDNA 的编码区包含在核小体耗尽的开放染色质内,该染色质具有高度转录活性。其次,组蛋白修饰不仅位于 rDNA 启动子处,还位于基因间间隔区内的新位点。第三,活性修饰的分布在不同细胞类型内部和之间比抑制性修饰更相似。第四,UBF 是 rRNA 转录的正调节因子,与整个基因组的位点结合。最后,绝缘体结合蛋白 CTCF 与 rDNA 的间隔启动子结合,表明转录绝缘在调节 rRNA 的转录中发挥作用。总而言之,这些分析证实并扩展了之前 rDNA ChIP 研究的结果,并为探索染色质介导的 rDNA 调控提供了新途径。
The transcription of ribosomal RNA (rRNA) is critical to life. Despite its importance, ribosomal DNA (rDNA) is not included in current genome assemblies and, consequently, genomic analyses to date have excluded rDNA. Here, we show that short sequence reads can be aligned to a genome assembly containing a single rDNA repeat. Integrated analysis of ChIP-seq, DNase-seq, MNase-seq and RNA-seq data reveals several novel findings. First, the coding region of active rDNA is contained within nucleosome-depleted open chromatin that is highly transcriptionally active. Second, histone modifications are located not only at the rDNA promoter but also at novel sites within the intergenic spacer. Third, the distributions of active modifications are more similar within and between different cell types than repressive modifications. Fourth, UBF, a positive regulator of rRNA transcription, binds to sites throughout the genome. Lastly, the insulator binding protein CTCF associates with the spacer promoter of rDNA, suggesting that transcriptional insulation plays a role in regulating the transcription of rRNA. Taken together, these analyses confirm and expand the results of previous ChIP studies of rDNA and provide novel avenues for exploration of chromatin-mediated regulation of rDNA.
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