Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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DOI：
10.1038/nature06008
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发表时间：
2007-08-02
期刊：
影响因子：
64.8
通讯作者：
Bernstein, Bradley E.
中科院分区：
文献类型：
--
作者：
Mikkelsen, Tarjei S.;Ku, Manching;Bernstein, Bradley E.
我们报告了基于单分子的测序技术在哺乳动物细胞中组蛋白修饰的高通量分析中的应用。通过从染色质免疫沉淀的DNA中获得超过40亿个序列，我们生成了小鼠胚胎干细胞，神经祖细胞和胚胎成纤维细胞的全基因组染色质态图。我们发现赖氨酸4和赖氨酸27三甲基化有效地区分了表达，有证明或稳定抑制的基因，因此反映了细胞态和谱系潜力。赖氨酸36三甲基化标志着原代编码和非编码转录本，促进基因注释。在卫星，端粒和活跃的长末端重复序列中检测到赖氨酸9和赖氨酸20的三甲基化，并可以扩散到近端独特序列中。赖氨酸4和赖氨酸9三甲基化标记标记控制区域。最后，我们表明可以使用单核苷酸多态性以等位基因特异性的方式读取染色质状态。这项研究为将综合染色质分析应用于不同哺乳动物细胞群体的表征提供了一个框架。
We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.