Reconstruction of enhancer–target networks in 935 samples of human primary cells, tissues and cell lines
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AbstractWe propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer–target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer–target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.
All Author(s) ListQin Cao, Christine Anyansi, Xihao Hu, Liangliang Xu, Lei Xiong, Wenshu Tang, Myth T S Mok, Chao Cheng, Xiaodan Fan, Mark Gerstein, Alfred S L Cheng, Kevin Y Yip
Journal nameNature Genetics
Year2017
Month10
Volume Number49
Issue Number10
PublisherNature Publishing Group
Pages1428 - 1436
ISSN1061-4036
eISSN1546-1718
LanguagesEnglish-United States
