Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

Mitchell Guttman, Ido Amit, Manuel Garber, Courtney French, Michael F. Lin, David Feldser, Maite Huarte, Or Zuk, Bryce W. Carey, John P. Cassady, Moran N. Cabili, Rudolf Jaenisch, Tarjei S. Mikkelsen, Tyler Jacks, Nir Hacohen, Bradley E. Bernstein, Manolis Kellis, Aviv Regev, John L. Rinn () and Eric S. Lander
Additional contact information
Mitchell Guttman: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Ido Amit: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Manuel Garber: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Courtney French: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Michael F. Lin: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
David Feldser: The Koch Institute for Integrative Cancer Research,
Maite Huarte: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Or Zuk: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Bryce W. Carey: Department of Biology,
John P. Cassady: Department of Biology,
Moran N. Cabili: Harvard Medical School, Boston, Massachusetts 02114, USA
Rudolf Jaenisch: Department of Biology,
Tarjei S. Mikkelsen: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Tyler Jacks: Department of Biology,
Nir Hacohen: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Bradley E. Bernstein: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Manolis Kellis: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Aviv Regev: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
John L. Rinn: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Eric S. Lander: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA

Nature, 2009, vol. 458, issue 7235, 223-227

Abstract: Large RNAs: conserved for a purpose Mammalian genomes are transcribed to produce numerous large non-coding RNAs, but their function is unclear, primarily because these transcripts show little or no evidence of evolutionary conservation. A new approach to characterizing these mysterious molecules has now moved the field on. Rather than targeting the RNA molecules themselves, their existence was revealed as chromatin modifications or epigenomic marks in the DNA of four mouse cell types. The search yielded over a thousand large multi-exonic transcriptional units that do not overlap known protein-coding loci and are highly conserved. Possible functions could be assigned to each of these large intervening non-coding RNAs (or lincRNAs), ranging from embryonic stem cell pluripotency to cell proliferation. Specific lincRNAs turn out to be regulated by transcription factors that are key in these processes including p53, NFκB, Sox2, Oct4, and Nanog — and most of these lincRNAs are conserved across mammals.

Date: 2009
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DOI: 10.1038/nature07672

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