Non-coding RNAs, especially lncRNAs, have emerged as key components in histone modification. The alterations in the epigenetic modifications of lncRNAs underlie some human disorders ranging from neurodegeneration to cancer. To characterize the epigenetic modifications of lncRNAs, we first constructed the histone modification maps of various epigenetic markers across different cell lines. Then, we developed a method to identify epigenetically regulated lncRNAs and their response genes by integrating large scale epigenetic and transcriptional profiles. Our results showed that epigenetic alterations at the promoters of lncRNAs can influence their expression and the negative response genes of most epigenetically regulated lncRNAs were enriched for PRC2-binding genes. At last, we inferred some lncRNAs with aberrant epigenetic modifications in glioblastoma and Alzheimer's disease, and proved that theses lncRNAs may contribute to the initiation of human diseases.
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