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Nat Struct Mol Biol DOI:10.1038/nsmb.2764

Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre.

Publication TypeJournal Article
Year of Publication2014
AuthorsHacisuleyman, E, Goff, LA, Trapnell, C, Williams, A, Henao-Mejia, J, Sun, L, McClanahan, P, Hendrickson, DG, Sauvageau, M, Kelley, DR, Morse, M, Engreitz, J, Lander, ES, Guttman, M, Lodish, HF, Flavell, R, Raj, A, Rinn, JL
JournalNat Struct Mol Biol
Date Published2014 Feb
KeywordsAnimals, Base Sequence, Chromatin, Chromosomes, Embryonic Stem Cells, Female, Humans, Male, Mice, Models, Genetic, Molecular Sequence Data, RNA, Long Noncoding, Sequence Analysis, RNA, X Chromosome Inactivation

RNA, including long noncoding RNA (lncRNA), is known to be an abundant and important structural component of the nuclear matrix. However, the molecular identities, functional roles and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear-matrix factor hnRNPU through a 156-bp repeating sequence and localizes across an ~5-Mb domain on the X chromosome. We further observed Firre localization across five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X chromosome. Both genetic deletion of the Firre locus and knockdown of hnRNPU resulted in loss of colocalization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes.


Alternate JournalNat. Struct. Mol. Biol.
PubMed ID24463464
PubMed Central IDPMC3950333
Grant List1DP20D008514 / DP / NCCDPHP CDC HHS / United States
DP2 OD006670 / OD / NIH HHS / United States
P01 GM099117 / GM / NIGMS NIH HHS / United States
1DP2OD00667 / OD / NIH HHS / United States
P01GM099117 / GM / NIGMS NIH HHS / United States
R01 DK068348 / DK / NIDDK NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DP2 OD008514 / OD / NIH HHS / United States
P50HG006193-01 / HG / NHGRI NIH HHS / United States
R01 DK047618 / DK / NIDDK NIH HHS / United States