Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
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DOI：
10.1038/ng1966
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Heintzman, Nathaniel D.;Stuart, Rhona K.;Ren, Bing
真核基因转录伴随着启动子附近核小体的乙酰化和甲基化，但基因组其他地方组蛋白修饰的位置和作用仍不清楚。我们以高分辨率测定了人类基因组 30 Mb 的染色质修饰状态，发现活性启动子由组蛋白 H3 (H3K4) 的 Lys4 三甲基化标记，而增强子由 H3K4 的单甲基化而非三甲基化标记。我们开发了计算算法，使用这些不同的染色质特征来识别新的调控元件，预测 30 Mb 区域内的 200 多个启动子和 400 个增强子。该方法以高灵敏度和特异性准确预测了独立鉴定的调控元件的位置和功能，并发现了肉碱转运蛋白 SLC22A5 (OCTN2) 的新型功能增强子。我们的结果深入了解了染色质修饰与转录调控活性之间的联系，并为人类基因组的功能注释提供了新工具。
Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome.