Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation.
Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation.
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DOI：
10.1093/hmg/ddv449
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发表时间：
2016-01-01
影响因子：
3.5
通讯作者：
Yi SV
中科院分区：
文献类型：
--
作者：
Mendizabal I;Yi SV
CpG岛（cgi）是人类基因组中研究最广泛的调控特征之一，在发育和疾病中起着关键作用。尽管有这样的意义和最初的表观遗传学定义，目前使用的CGI集通常是从DNA序列特征预测的。尽管gis在DNA甲基化的实际分析中有着深刻的影响，但最近的研究表明，这种计算注释存在不准确性。在这里，我们使用来自10个不同人体组织的亚硫酸氢盐全基因组测序来鉴定一个全面的、实验获得的、单碱基分辨率的CGI目录。除了无与伦比的注释精度外，我们的方法还不受任意序列特征或探针亲和差异的潜在偏差的影响。除了澄清广泛使用的加州大学圣克鲁兹分校（UCSC）注释中的大量假阳性外，我们的研究还确定了许多新的表观遗传位点。特别是，我们揭示了转座元件对人类基因组表观遗传调控景观的重要影响，并证明了转录起始在cgi中普遍存在，包括基因体中的替代启动子和基因间区域的非编码rna。此外，协调的DNA甲基化和染色质修饰在新的cgi中标记了组织特异性增强子。通过ChIP-seq富集特异性转录因子结合，支持了cgi在组织特异性转录调控中的机制作用。新的CGI目录提供了一个全面和集成的表遗传调控的基因组热点列表。
CpG islands (CGIs) are one of the most widely studied regulatory features of the human genome, with critical roles in development and disease. Despite such significance and the original epigenetic definition, currently used CGI sets are typically predicted from DNA sequence characteristics. Although CGIs are deeply implicated in practical analyses of DNA methylation, recent studies have shown that such computational annotations suffer from inaccuracies. Here we used whole-genome bisulfite sequencing from 10 diverse human tissues to identify a comprehensive, experimentally obtained, single-base resolution CGI catalog. In addition to the unparalleled annotation precision, our method is free from potential bias due to arbitrary sequence features or probe affinity differences. In addition to clarifying substantial false positives in the widely used University of California Santa Cruz (UCSC) annotations, our study identifies numerous novel epigenetic loci. In particular, we reveal significant impact of transposable elements on the epigenetic regulatory landscape of the human genome and demonstrate ubiquitous presence of transcription initiation at CGIs, including alternative promoters in gene bodies and non-coding RNAs in intergenic regions. Moreover, coordinated DNA methylation and chromatin modifications mark tissue-specific enhancers at novel CGIs. Enrichment of specific transcription factor binding from ChIP-seq supports mechanistic roles of CGIs on the regulation of tissue-specific transcription. The new CGI catalog provides a comprehensive and integrated list of genomic hotspots of epigenetic regulation.