组蛋白H3赖氨酸4和27三甲基化的全基因组图谱揭示了人类胚胎干细胞中不同的基因组区域。

Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells.

作者信息

Zhao Xiao Dong, Han Xu, Chew Joon Lin, Liu Jun, Chiu Kuo Ping, Choo Andre, Orlov Yuriy L, Sung Wing-Kin, Shahab Atif, Kuznetsov Vladimir A, Bourque Guillaume, Oh Steve, Ruan Yijun, Ng Huck-Hui, Wei Chia-Lin

机构信息

Genome Technology and Biology Group, Genome Institute of Singapore, 138672, Singapore.

出版信息

Cell Stem Cell. 2007 Sep 13;1(3):286-98. doi: 10.1016/j.stem.2007.08.004.

DOI:10.1016/j.stem.2007.08.004

PMID:18371363

Abstract

Epigenetic modifications are crucial for proper lineage specification and embryo development. To explore the chromatin modification landscapes in human ES cells, we profiled two histone modifications, H3K4me3 and H3K27me3, by ChIP coupled with the paired-end ditags sequencing strategy. H3K4me3 was found to be a prevalent mark and occurred in close proximity to the promoters of two-thirds of total human genes. Among the H3K27me3 loci identified, 56% are associated with promoters and the vast majority of them are comodified by H3K4me3. By deep-transcript digital counting, 80% of H3K4me3 and 36% of comodified promoters were found to be transcribed. Remarkably, we observed that different combinations of histone methylations are associated with genes from distinct functional categories. These global histone methylation maps provide an epigenetic framework that enables the discovery of novel transcriptional networks and delineation of different genetic compartments of the pluripotent cell genome.

摘要

表观遗传修饰对于正确的谱系特化和胚胎发育至关重要。为了探索人类胚胎干细胞中的染色质修饰图谱，我们通过染色质免疫沉淀结合双末端标签测序策略，对两种组蛋白修饰H3K4me3和H3K27me3进行了分析。发现H3K4me3是一种普遍存在的标记，出现在三分之二的人类基因启动子附近。在鉴定出的H3K27me3位点中，56%与启动子相关，其中绝大多数同时被H3K4me3修饰。通过深度转录本数字计数，发现80%的H3K4me3和36%的共修饰启动子被转录。值得注意的是，我们观察到组蛋白甲基化的不同组合与不同功能类别的基因相关。这些全局组蛋白甲基化图谱提供了一个表观遗传框架，有助于发现新的转录网络并描绘多能细胞基因组的不同遗传区域。