Koch Christoph M, Andrews Robert M, Flicek Paul, Dillon Shane C, Karaöz Ulaş, Clelland Gayle K, Wilcox Sarah, Beare David M, Fowler Joanna C, Couttet Phillippe, James Keith D, Lefebvre Gregory C, Bruce Alexander W, Dovey Oliver M, Ellis Peter D, Dhami Pawandeep, Langford Cordelia F, Weng Zhiping, Birney Ewan, Carter Nigel P, Vetrie David, Dunham Ian
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB101SA, United Kingdom.
Genome Res. 2007 Jun;17(6):691-707. doi: 10.1101/gr.5704207.
We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including the ENCODE Consortium common cell lines GM06990 (lymphoblastoid) and HeLa-S3, as well as K562, HFL-1, and MOLT4, we identified clear patterns of histone modification profiles with respect to genomic features. H3K4me3, H3K4me2, and H3ac modifications are tightly associated with the transcriptional start sites (TSSs) of genes, while H3K4me1 and H4ac have more widespread distributions. TSSs reveal characteristic patterns of both types of modification present and the position relative to TSSs. These patterns differ between active and inactive genes and in particular the state of H3K4me3 and H3ac modifications is highly predictive of gene activity. Away from TSSs, modification sites are enriched in H3K4me1 and relatively depleted in H3K4me3 and H3ac. Comparison between cell lines identified differences in the histone modification profiles associated with transcriptional differences between the cell lines. These results provide an overview of the functional relationship among histone modifications and gene expression in human cells.
我们生成了全基因组编码区域组蛋白H3赖氨酸9/14乙酰化（H3ac）、组蛋白H4赖氨酸5/8/12/16乙酰化（H4ac）以及组蛋白H3赖氨酸4单甲基化、二甲基化和三甲基化（分别为H3K4me1、H3K4me2、H3K4me3）的高分辨率图谱。通过研究包括基因组编码计划联盟通用细胞系GM06990（淋巴母细胞样）和HeLa-S3，以及K562、HFL-1和MOLT4在内的五种人类细胞系中的每种修饰，我们确定了与基因组特征相关的组蛋白修饰谱的清晰模式。H3K4me3、H3K4me2和H3ac修饰与基因的转录起始位点（TSS）紧密相关，而H3K4me1和H4ac具有更广泛的分布。TSS揭示了两种修饰的特征模式以及相对于TSS的位置。这些模式在活跃基因和非活跃基因之间存在差异，特别是H3K4me3和H3ac修饰的状态高度预测基因活性。在远离TSS的区域，修饰位点富含H3K4me1，而H3K4me3和H3ac相对较少。细胞系之间的比较确定了与细胞系转录差异相关的组蛋白修饰谱的差异。这些结果概述了人类细胞中组蛋白修饰与基因表达之间的功能关系。
