The landscape of histone modifications across 1% of the human genome in five human cell lines
The landscape of histone modifications across 1% of the human genome in five human cell lines
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DOI：
10.1101/gr.5704207
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发表时间：
2007-06-01
期刊：
影响因子：
7
通讯作者：
Dunham, Ian
中科院分区：
文献类型：
--
作者：
Koch, Christoph M.;Andrews, Robert M.;Dunham, Ian
我们生成了组蛋白H3赖氨酸9/14乙酰化（H3 ac），组蛋白H4赖氨酸5/8/12/16乙酰化（H4 ac）和组蛋白H3在赖氨酸4单，二和三甲基化（H3 K4 me 1，H3 K4 me 2，H3 K4 me 3，分别）的高分辨率地图。研究了5种人类细胞系中的每种修饰，包括ENCODE Consortium常见细胞系GM 06990（类淋巴母细胞）和HeLa-S3，以及K562，HFL-1和MOLT 4，我们确定了组蛋白修饰谱的基因组特征的清晰模式。H3 K4 me 3、H3 K4 me 2和H3 ac修饰与基因的转录起始位点（TSS）紧密相关，而H3 K4 me 1和H4 ac具有更广泛的分布。TSS揭示了两种类型的修改存在的特征模式和相对于TSS的位置。这些模式在活性和非活性基因之间不同，特别是H3 K4 me 3和H3 ac修饰的状态高度预测基因活性。远离TSS，修饰位点富含H3 K4 me 1，而相对缺乏H3 K4 me 3和H3 ac。细胞系之间的比较确定了与细胞系之间的转录差异相关的组蛋白修饰谱的差异。这些结果提供了人类细胞中组蛋白修饰和基因表达之间的功能关系的概述。
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.