An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment
An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment
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DOI：
10.1038/emboj.2011.399
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发表时间：
2012-01-18
期刊：
影响因子：
11.4
通讯作者：
Higgs, Douglas R.
中科院分区：
文献类型：
--
作者：
Lynch, Magnus D.;Smith, Andrew J. H.;Higgs, Douglas R.
DNA序列在决定染色质状态中的作用还不完全清楚。我们以前已经证明，人类细胞的大染色体片段在小鼠细胞中重演了它们的天然染色质状态，但局部序列与它们的基因组背景的相对贡献仍然未知。在这项研究中，我们比较了orthopathic染色体区域，其中人类基因座建立了多能干细胞中Polycomb复合物招募的突出位点，而相应的小鼠基因座则没有。使用重组介导的盒交换在小鼠基因座，我们建立了在染色质状态的编码的本地序列的首要地位。我们发现，染色质二价的信号是冗余编码的二价结构域，这反映了Polycomb复合物的招聘和转录激活之间的竞争。此外，我们的研究结果表明，高密度的未甲基化的CpG二核苷酸是足够的脊椎动物Polycomb招聘。该模型得到了DNA甲基转移酶缺陷胚胎干细胞分析的支持。The EMBO Journal（2012）31，317-329. doi：10.1038/daj.2011.399; 2011年11月4日在线发布
The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyl-transferase-deficient embryonic stem cells. The EMBO Journal (2012) 31, 317-329. doi:10.1038/emboj.2011.399; Published online 4 November 2011