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Cell Rep. 2015 Aug 18;12(7):1089-98. doi: 10.1016/j.celrep.2015.07.033. Epub 2015 Aug 6.

Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes.

Author information

1
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
2
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: aruthenburg@uchicago.edu.

Abstract

A number of long noncoding RNAs (lncRNAs) have been reported to regulate transcription via recruitment of chromatin modifiers or bridging distal enhancer elements to gene promoters. However, the generality of these modes of regulation and the mechanisms of chromatin attachment for thousands of unstudied human lncRNAs remain unclear. To address these questions, we performed stringent nuclear fractionation coupled to RNA sequencing. We provide genome-wide identification of human chromatin-associated lncRNAs and demonstrate tethering of RNA to chromatin by RNAPII is a pervasive mechanism of attachment. We also uncovered thousands of chromatin-enriched RNAs (cheRNAs) that share molecular properties with known lncRNAs. Although distinct from eRNAs derived from active prototypical enhancers, the production of cheRNAs is strongly correlated with the expression of neighboring protein-coding genes. This work provides an updated framework for nuclear RNA organization that includes a large chromatin-associated transcript population correlated with active genes and may prove useful in de novo enhancer annotation.

PMID:
26257179
PMCID:
PMC5697714
DOI:
10.1016/j.celrep.2015.07.033
[Indexed for MEDLINE]
Free PMC Article

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