Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre.
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.
1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [3] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [4].
Ezgi
E
Hacisuleyman
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [3] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4].
Loyal A
LA
Goff
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Cole
C
Trapnell
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Adam
A
Williams
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Jorge
J
Henao-Mejia
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Lei
L
Sun
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Patrick
P
McClanahan
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
David G
DG
Hendrickson
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Martin
M
Sauvageau
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
David R
DR
Kelley
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Michael
M
Morse
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Jesse
J
Engreitz
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Eric S
ES
Lander
Department of Biology, California Institute of Technology, Pasadena, California, USA.
Mitch
M
Guttman
1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Harvey F
HF
Lodish
1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
Richard
R
Flavell
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Arjun
A
Raj
1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [3] Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
John L
JL
Rinn
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D053595:Embryonic Stem Cells; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D062085:RNA, Long Noncoding / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D017423:Sequence Analysis, RNA; D049951:X Chromosome Inactivation
D002843:Chromatin; D062085:RNA, Long Noncoding; C000609475:long noncoding RNA Firre, human