人类基因组中组蛋白甲基化的高分辨率分析。

High-resolution profiling of histone methylations in the human genome.

作者信息

Barski Artem, Cuddapah Suresh, Cui Kairong, Roh Tae-Young, Schones Dustin E, Wang Zhibin, Wei Gang, Chepelev Iouri, Zhao Keji

机构信息

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.

出版信息

Cell. 2007 May 18;129(4):823-37. doi: 10.1016/j.cell.2007.05.009.

DOI:10.1016/j.cell.2007.05.009

PMID:17512414

Abstract

Histone modifications are implicated in influencing gene expression. We have generated high-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology. Typical patterns of histone methylations exhibited at promoters, insulators, enhancers, and transcribed regions are identified. The monomethylations of H3K27, H3K9, H4K20, H3K79, and H2BK5 are all linked to gene activation, whereas trimethylations of H3K27, H3K9, and H3K79 are linked to repression. H2A.Z associates with functional regulatory elements, and CTCF marks boundaries of histone methylation domains. Chromosome banding patterns are correlated with unique patterns of histone modifications. Chromosome breakpoints detected in T cell cancers frequently reside in chromatin regions associated with H3K4 methylations. Our data provide new insights into the function of histone methylation and chromatin organization in genome function.

摘要

组蛋白修饰与基因表达的调控有关。我们利用Solexa 1G测序技术，绘制了全人类基因组范围内20种组蛋白赖氨酸和精氨酸甲基化、组蛋白变体H2A.Z、RNA聚合酶II以及绝缘子结合蛋白CTCF分布的高分辨率图谱。我们还确定了在启动子、绝缘子、增强子和转录区域出现的典型组蛋白甲基化模式。H3K27、H3K9、H4K20、H3K79和H2BK5的单甲基化均与基因激活相关，而H3K27、H3K9和H3K79的三甲基化则与基因抑制相关。H2A.Z与功能性调控元件相关联，而CTCF则标记了组蛋白甲基化结构域的边界。染色体带型与独特的组蛋白修饰模式相关。在T细胞癌中检测到的染色体断点通常位于与H3K4甲基化相关的染色质区域。我们的数据为组蛋白甲基化和染色质组织在基因组功能中的作用提供了新的见解。