Genomic characterization of the mouse ribosomal DNA locus.

Genomic characterization of the mouse ribosomal DNA locus.
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DOI:
10.1534/g3.113.009290
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发表时间:
2014-02-19
期刊:
G3 (Bethesda, Md.)
影响因子:
--
通讯作者:
Scacheri PC
Scacheri PC
中科院分区:
其他
文献类型:
--
作者:
Zentner GE;Balow SA;Scacheri PC

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RRNA的转录对所有活细胞都是至关重要的,并在染色质结构水平上受到严格控制。尽管包括染色质免疫沉淀和大规模并行短读测序(CHIP-SEQ)在内的基因组技术的广泛采用使得在全基因组范围内对染色质结构的询问成为可能,但直到最近,rDNA还没有通过这种技术进行分析。我们将rDNA的基因组分析扩展到小鼠(Mus Musculus),其中rDNA与人的rDNA在结构上相似,但在序列上存在很大的差异。比较小鼠胚胎干细胞(MESCs)和分化程度较高的小鼠细胞类型的rDNA组蛋白标记,发现在多能状态和分化状态下的差异。我们还观察到mESCs和人类胚胎干细胞(HESCs)在rDNA组蛋白修饰模式上的显著差异。令人惊讶的是,我们发现多能因子OCT4在mESCs和hESCs中以相似的模式与rDNA结合。扩展这一分析,我们发现另外17个多能相关因子与mESCs中的rDNA结合,这表明在多能细胞中rDNA调节的新模式。综上所述,我们的结果提供了一个重要模型系统中rDNA染色质结构的详细视图,并使高分辨率比较小鼠和人类之间的rDNA调控成为可能。
The transcription of rRNA is critical to all living cells and is tightly controlled at the level of chromatin structure. Although the widespread adoption of genomic technologies including chromatin immunoprecipitation with massively parallel short-read sequencing (ChIP-seq) has allowed for the interrogation of chromatin structure on a genome-wide scale, until recently rDNA has not been analyzed by this technique. We extended genomic analysis of rDNA to mouse (Mus musculus), in which rDNA is similar in structure but highly divergent in sequence compared with human rDNA. Comparison of rDNA histone marks between mouse embryonic stem cells (mESCs) and more differentiated mouse cell types revealed differences between pluripotent and differentiated states. We also observed substantial divergence in rDNA histone modification patterns between mESCs and human embryonic stem cells (hESCs). Surprisingly, we found that the pluripotency factor OCT4 was bound to rDNA in similar patterns in mESCs and hESCs. Extending this analysis, we found that an additional 17 pluripotency-associated factors were bound to rDNA in mESCs, suggesting novel modes of rDNA regulation in pluripotent cells. Taken together, our results provide a detailed view of rDNA chromatin structure in an important model system and enable high-resolution comparison of rDNA regulation between mouse and human.
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