期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 43, 页码 15613-15622出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.008732
关键词
long noncoding RNA (long ncRNA; lncRNA); chromatin modification; epigenetics; gene regulation; transcription enhancer; survival
资金
- National Key R&D Program of China [2018YFC2000100]
- National Natural Science Foundation of China [31871336, 61873075, 61573122]
- special funds for the construction of higher education in Heilongjiang Province [UNPYSCT2016049]
- Graduate Innovation Funds of Harbin Medical University [YJSCX2016-14HYD]
Over the past decade, thousands of long noncoding RNAs (lncRNAs) have been identified, many of which play crucial roles in normal physiology and human disease. LncRNAs can interact with chromatin and then recruit protein complexes to remodel chromatin states, thus regulating gene expression. However, how lncRNA-chromatin interactions contribute to their biological functions is largely unknown. Here, we collected and constructed an atlas of 188,647 lncRNA-chromatin interactions in human and mouse. All lncRNAs showed diverse epigenetic modification patterns at their binding sites, especially the marks of enhancer activity. Functional analysis of lncRNA target genes further revealed that lncRNAs could exert their functions by binding to both promoter and distal regulatory elements, especially the distal regulatory elements. Intriguingly, many important pathways were observed to be widely regulated by lncRNAs through distal binding. For example, NEAT1, a cancer lncRNA, controls 13.3% of genes in the PI3K-AKT signaling pathway by interacting with distal regulatory elements. In addition, ?two-gene? signatures composed of a lncRNA and its distal target genes, such as HOTAIR-CRIM1, provided significant clinical benefits relative to the lncRNA alone. In summary, our findings underscored that lncRNA-distal interactions were essential for lncRNA functions, which would provide new clues to understand the molecular mechanisms of lncRNAs in complex disease.
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