Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs

Nat Commun. 2015 Feb 18:6:6370. doi: 10.1038/ncomms7370.


Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, we determine tissue-specific epigenetic regulation for 3,753 (69% examined) lincRNAs, with 54% active in one of the 14 cell/tissue clusters and an additional 15% in two or three clusters. A larger fraction of lincRNA TSSs is marked in a tissue-specific manner by H3K4me1 than by H3K4me3. The tissue-specific lincRNAs are strongly linked to tissue-specific pathways and undergo distinct chromatin state transitions during cellular differentiation. Polycomb-regulated lincRNAs reside in the bivalent state in embryonic stem cells and many of them undergo H3K27me3-mediated silencing at early stages of differentiation. The exquisitely tissue-specific epigenetic regulation of lincRNAs and the assignment of a majority of them to specific tissue types will inform future studies of this newly discovered class of genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation*
  • Embryonic Stem Cells / physiology
  • Epigenesis, Genetic*
  • Epigenomics*
  • Humans
  • Organ Specificity
  • Phenotype
  • Polycomb-Group Proteins / physiology
  • RNA, Long Noncoding / metabolism*
  • Regulatory Elements, Transcriptional*


  • Polycomb-Group Proteins
  • RNA, Long Noncoding

Associated data

  • GEO/GSE16256
  • GEO/GSE16368
  • GEO/GSE17312
  • GEO/GSE18927
  • GEO/GSE19465
  • GEO/GSE25246
  • GEO/GSE25247
  • GEO/GSE25248
  • GEO/GSE25249