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

Viren Amin, R. Alan Harris, Vitor Onuchic, Andrew R. Jackson, Tim Charnecki, Sameer Paithankar, Sai Lakshmi Subramanian, Kevin Riehle, Cristian Coarfa () and Aleksandar Milosavljevic ()
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Viren Amin: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
R. Alan Harris: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Vitor Onuchic: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Andrew R. Jackson: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Tim Charnecki: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Sameer Paithankar: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Sai Lakshmi Subramanian: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Kevin Riehle: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Cristian Coarfa: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine
Aleksandar Milosavljevic: Epigenome Center, Bioinformatics Research Laboratory, Genetics, Baylor College of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7370

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