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Published December 2016 | Supplemental Material
Journal Article Open

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Abstract

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus.

Additional Information

© 2016 Macmillan Publishers Limited, part of Springer Nature. Published online 26 October 2016. We thank members of the Guttman laboratory, especially Sofia Quinodoz, for helpful discussions, and Sigrid Knemeyer for help with the figures. J.M.E. is supported by the Fannie and John Hertz Foundation and the Broad Institute. N.O. is supported by a postdoctoral fellowship from the California Institute of Technology. M.G. is a New York Stem Cell Foundation Robertson Investigator, an investigator at the Heritage Medical Research Institute, a Searle Scholar, a Pew-Steward scholar and an Alfred P. Sloan fellow. Research in the Guttman laboratory is funded by the National Institutes of Health (NIH) 4DN programme, an NIH Director's Early Independence Award, the New York Stem Cell Foundation, the Edward Mallinckrodt Foundation, Sontag Foundation, Searle Scholars Program, Pew-Steward Scholars programme and funds from the California Institute of Technology. These authors contributed equally to this work: Jesse M. Engreitz & Noah Ollikainen. The authors declare no competing interests.

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