Chromatin and RNA Maps Reveal Regulatory Long Noncoding RNAs in Mouse

Mol Cell Biol. 2015 Dec 28;36(5):809-19. doi: 10.1128/MCB.00955-15.

Abstract

Discovering and classifying long noncoding RNAs (lncRNAs) across all mammalian tissues and cell lines remains a major challenge. Previously, mouse lncRNAs were identified using transcriptome sequencing (RNA-seq) data from a limited number of tissues or cell lines. Additionally, associating a few hundred lncRNA promoters with chromatin states in a single mouse cell line has identified two classes of chromatin-associated lncRNA. However, the discovery and classification of lncRNAs is still pending in many other tissues in mouse. To address this, we built a comprehensive catalog of lncRNAs by combining known lncRNAs with high-confidence novel lncRNAs identified by mapping and de novo assembling billions of RNA-seq reads from eight tissues and a primary cell line in mouse. Next, we integrated this catalog of lncRNAs with multiple genome-wide chromatin state maps and found two different classes of chromatin state-associated lncRNAs, including promoter-associated (plncRNAs) and enhancer-associated (elncRNAs) lncRNAs, across various tissues. Experimental knockdown of an elncRNA resulted in the downregulation of the neighboring protein-coding Kdm8 gene, encoding a histone demethylase. Our findings provide 2,803 novel lncRNAs and a comprehensive catalog of chromatin-associated lncRNAs across different tissues in mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics*
  • Chromosome Mapping
  • Gene Expression Profiling
  • Mice / genetics*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA
  • Transcriptome

Substances

  • Chromatin
  • RNA, Long Noncoding