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

Nature Structural & Molecular Biology volume 21, pages 198–206 (2014)Cite this article

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Abstract

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.

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Figure 1: Firre is a new X-chromosome–localized lincRNA.
Figure 2: Firre is a new, strictly nuclear lincRNA that escapes X-chromosome inactivation.
Figure 3: Firre forms cis and trans chromosomal contacts.
Figure 4: The trans-chromosomal contacts of Firre are colocalized within the nucleus.
Figure 5: Characterization of Firre knockout in male mESCs.
Figure 6: hnRNPU binds to the RRD of Firre and regulates its nuclear localization.
Figure 7: The trans-chromosomal contacts of Firre are mediated via its interaction with the nuclear-matrix protein hnRNPU.

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References

  1. Huarte, M. & Rinn, J.L. Large non-coding RNAs: missing links in cancer? Hum. Mol. Genet. 19, R152–R161 (2010).

    Article  CAS  Google Scholar 

  2. Rinn, J.L. & Chang, H.Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145–166 (2012).

    Article  CAS  Google Scholar 

  3. Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005).

    Article  CAS  Google Scholar 

  4. Derrien, T. et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775–1789 (2012).

    Article  CAS  Google Scholar 

  5. Batista, P.J. & Chang, H.Y. Cytotopic localization by long noncoding RNAs. Curr. Opin. Cell Biol. 25, 195–199 (2013).

    Article  CAS  Google Scholar 

  6. Guttman, M. & Rinn, J.L. Modular regulatory principles of large non-coding RNAs. Nature 482, 339–346 (2012).

    Article  CAS  Google Scholar 

  7. Clemson, C.M. et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol. Cell 33, 717–726 (2009).

    Article  CAS  Google Scholar 

  8. Maass, P.G. et al. A misplaced lncRNA causes brachydactyly in humans. J. Clin. Invest. 122, 3990–4002 (2012).

    Article  CAS  Google Scholar 

  9. Nie, L. et al. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am. J. Transl. Res. 4, 127–150 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Pandey, R.R. et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell 32, 232–246 (2008).

    Article  CAS  Google Scholar 

  11. Rinn, J.L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323 (2007).

    Article  CAS  Google Scholar 

  12. Tsai, M.C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329, 689–693 (2010).

    Article  CAS  Google Scholar 

  13. Vallot, C. et al. XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells. Nat. Genet. 45, 239–241 (2013).

    Article  CAS  Google Scholar 

  14. Zhao, J., Sun, B.K., Erwin, J.A., Song, J.J. & Lee, J.T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756 (2008).

    Article  CAS  Google Scholar 

  15. Kaneko, S., Son, J., Shen, S.S., Reinberg, D. & Bonasio, R. PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat. Struct. Mol. Biol. 20, 1258–1264 (2013).

    Article  CAS  Google Scholar 

  16. Davidovich, C., Zheng, L., Goodrich, K.J. & Cech, T.R. Promiscuous RNA binding by Polycomb repressive complex 2. Nat. Struct. Mol. Biol. 20, 1250–1257 (2013).

    Article  CAS  Google Scholar 

  17. Jeon, Y., Sarma, K. & Lee, J.T. New and Xisting regulatory mechanisms of X chromosome inactivation. Curr. Opin. Genet. Dev. 22, 62–71 (2012).

    Article  CAS  Google Scholar 

  18. Plath, K., Mlynarczyk-Evans, S., Nusinow, D.A. & Panning, B. Xist RNA and the mechanism of X chromosome inactivation. Annu. Rev. Genet. 36, 233–278 (2002).

    Article  CAS  Google Scholar 

  19. Engreitz, J.M. et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341, 1237973 (2013).

    Article  Google Scholar 

  20. Simon, M.D. et al. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 504, 465–469 (2013).

    Article  CAS  Google Scholar 

  21. Bouvier, D., Hubert, J., Seve, A.P. & Bouteille, M. Nuclear RNA-associated proteins and their relationship to the nuclear matrix and related structures in HeLa-cells. Can. J. Biochem. Cell Biol. 63, 631–643 (1985).

    Article  CAS  Google Scholar 

  22. Nickerson, J.A., Krochmalnic, G., Wan, K.M. & Penman, S. Chromatin architecture and nuclear RNA. Proc. Natl. Acad. Sci. USA 86, 177–181 (1989).

    Article  CAS  Google Scholar 

  23. Pederson, T. & Bhorjee, J.S. Evidence for a role of RNA in eukaryotic chromosome structure: metabolically stable, small nuclear RNA species are covalently linked to chromosomal DNA in HeLa cells. J. Mol. Biol. 128, 451–480 (1979).

    Article  CAS  Google Scholar 

  24. Umlauf, D., Fraser, P. & Nagano, T. The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme. Biol. Chem. 389, 323–331 (2008).

    Article  CAS  Google Scholar 

  25. Wilusz, J.E., Sunwoo, H. & Spector, D.L. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494–1504 (2009).

    Article  CAS  Google Scholar 

  26. Mao, Y.S., Sunwoo, H., Zhang, B. & Spector, D.L. Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat. Cell Biol. 13, 95–101 (2011).

    Article  CAS  Google Scholar 

  27. Delpretti, S. et al. Multiple enhancers regulate Hoxd genes and the Hotdog lncRNA during cecum budding. Cell Rep. 5, 137–150 (2013).

    Article  CAS  Google Scholar 

  28. Sun, L. et al. Long noncoding RNAs regulate adipogenesis. Proc. Natl. Acad. Sci. USA 110, 3387–3392 (2013).

    Article  CAS  Google Scholar 

  29. Raj, A., van den Bogaard, P., Rifkin, S.A., van Oudenaarden, A. & Tyagi, S. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5, 877–879 (2008).

    Article  CAS  Google Scholar 

  30. Cuddapah, S. et al. Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res. 19, 24–32 (2009).

    Article  CAS  Google Scholar 

  31. Chu, C., Quinn, J. & Chang, H.Y. Chromatin isolation by RNA purification (ChIRP). J. Vis. Exp. 61, 3912 (2012).

    Google Scholar 

  32. Simon, M.D. et al. The genomic binding sites of a noncoding RNA. Proc. Natl. Acad. Sci. USA 108, 20497–20502 (2011).

    Article  CAS  Google Scholar 

  33. Mariner, P.D. et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol. Cell 29, 499–509 (2008).

    Article  CAS  Google Scholar 

  34. Lee, E.K. et al. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor γ expression. Mol. Cell. Biol. 31, 626–638 (2011).

    Article  CAS  Google Scholar 

  35. Nukitrangsan, N. et al. Effect of Peucedanum japonicum Thunb on the expression of obesity-related genes in mice on a high-fat diet. J. Oleo Sci. 60, 527–536 (2011).

    Article  CAS  Google Scholar 

  36. Rubi, B., del Arco, A., Bartley, C., Satrustegui, J. & Maechler, P. The malate-aspartate NADH shuttle member Aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in beta cells. J. Biol. Chem. 279, 55659–55666 (2004).

    Article  CAS  Google Scholar 

  37. Seo, J. et al. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes 58, 2565–2573 (2009).

    Article  CAS  Google Scholar 

  38. Choy, L. & Derynck, R. Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J. Biol. Chem. 278, 9609–9619 (2003).

    Article  CAS  Google Scholar 

  39. Göhring, F. & Fackelmayer, F.O. The scaffold/matrix attachment region binding protein hnRNP-U (SAF-A) is directly bound to chromosomal DNA in vivo: a chemical cross-linking study. Biochemistry 36, 8276–8283 (1997).

    Article  Google Scholar 

  40. Hasegawa, Y. et al. The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev. Cell 19, 469–476 (2010).

    Article  CAS  Google Scholar 

  41. Lobov, I.B., Tsutsui, K., Mitchell, A.R. & Podgornaya, O.I. Specificity of SAF-A and lamin B binding in vitro correlates with the satellite DNA bending state. J. Cell. Biochem. 83, 218–229 (2001).

    Article  CAS  Google Scholar 

  42. Huelga, S.C. et al. Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins. Cell Rep. 1, 167–178 (2012).

    Article  CAS  Google Scholar 

  43. Xiao, R. et al. Nuclear matrix factor hnRNP U/SAF-A exerts a global control of alternative splicing by regulating U2 snRNP maturation. Mol. Cell 45, 656–668 (2012).

    Article  CAS  Google Scholar 

  44. Wong, L.H. et al. Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res. 17, 1146–1160 (2007).

    Article  CAS  Google Scholar 

  45. Merico, D., Isserlin, R., Stueker, O., Emili, A. & Bader, G.D. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5, e13984 (2010).

    Article  Google Scholar 

  46. Lee, B.K. & Iyer, V.R. Genome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation. J. Biol. Chem. 287, 30906–30913 (2012).

    Article  CAS  Google Scholar 

  47. Price, A.L., Jones, N.C. & Pevzner, P.A. De novo identification of repeat families in large genomes. Bioinformatics 21 (suppl. 1), i351–i358 (2005).

    Article  CAS  Google Scholar 

  48. Donohoe, M.E., Silva, S.S., Pinter, S.F., Xu, N. & Lee, J.T. The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature 460, 128–132 (2009).

    Article  CAS  Google Scholar 

  49. Kent, W.J. BLAT: the BLAST-like alignment tool. Genome Res. 12, 656–664 (2002).

    Article  CAS  Google Scholar 

  50. Bradley, R.K. et al. Fast statistical alignment. PloS Comput. Biol. 5, e1000392 (2009).

    Article  Google Scholar 

  51. Arlotta, P. et al. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron 45, 207–221 (2005).

    Article  CAS  Google Scholar 

  52. Tiveron, M.C., Hirsch, M.R. & Brunet, J.F. The expression pattern of the transcription factor Phox2 delineates synaptic pathways of the autonomic nervous system. J. Neurosci. 16, 7649–7660 (1996).

    Article  CAS  Google Scholar 

  53. Guttman, M. et al. Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat. Biotechnol. 28, 503–510 (2010).

    Article  CAS  Google Scholar 

  54. Quinlan, A.R. & Hall, I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    Article  CAS  Google Scholar 

  55. Vizlin-Hodzic, D., Johansson, H., Ryme, J., Simonsson, T. & Simonsson, S. SAF-A has a role in transcriptional regulation of Oct4 in ES cells through promoter binding. Cell. Reprogram. 13, 13–27 (2011).

    Article  CAS  Google Scholar 

  56. Trapnell, C. et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562–578 (2012).

    Article  CAS  Google Scholar 

  57. Kelley, D. & Rinn, J. Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol. 13, R107 (2012).

    Article  Google Scholar 

  58. Trapnell, C., Pachter, L. & Salzberg, S.L. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111 (2009).

    Article  CAS  Google Scholar 

  59. Trapnell, C. et al. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat. Biotechnol. 31, 46–53 (2013).

    Article  CAS  Google Scholar 

  60. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Biosearch, especially M. Beal, H. Johansson, A. Orjalo, S. Coassin and R. Cook, for materials, advice and help with FISH experiments. We are grateful to the entire Rinn and Raj laboratories for generous help with experiments, bioinformatics and preparation of the manuscript. This work was supported by US National Institutes of Health grants 1DP2OD00667 (J.L.R.), P01GM099117 (J.L.R.), 1DP20D008514 (A.R.) and P50HG006193-01 (J.L.R.) and by the Howard Hughes Medical Institute (R.F.).

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Author notes

  1. Ezgi Hacisuleyman and Loyal A Goff: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA

    Ezgi Hacisuleyman

  2. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA

    Ezgi Hacisuleyman, Loyal A Goff, Cole Trapnell, David G Hendrickson, Martin Sauvageau, David R Kelley & John L Rinn

  3. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA

    Ezgi Hacisuleyman, Loyal A Goff, Cole Trapnell, David G Hendrickson, Martin Sauvageau, David R Kelley, Michael Morse, Jesse Engreitz, Eric S Lander & John L Rinn

  4. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Loyal A Goff

  5. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Adam Williams, Jorge Henao-Mejia & Richard Flavell

  6. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA

    Lei Sun & Harvey F Lodish

  7. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Patrick McClanahan & Arjun Raj

  8. Department of Biology, California Institute of Technology, Pasadena, California, USA

    Mitch Guttman

  9. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Harvey F Lodish

  10. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Harvey F Lodish

  11. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

    Richard Flavell

  12. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

    John L Rinn

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Contributions

E.H. designed and performed experiments. L.A.G. performed computational analysis. J.L.R. directed research. E.H., L.A.G. and J.L.R. wrote the manuscript. C.T. and D.R.K. helped with computational analysis. M.S., D.G.H., P.M., J.E., M.G., A.R., M.M. and E.S.L. contributed experiments. A.W., J.H.-M. and R.F. generated knockout mESCs. L.S. and H.F.L. helped with experimental techniques.

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Correspondence to John L Rinn.

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Integrated supplementary information

Supplementary Figure 1 Firre is a stable transcript.

(a) Cloning of 50 different mouse isoforms of Firre, with most exons demarcated by the inclusion of the repeat domain RRD (purple tracks). (b) The isoform assemblies for human FIRRE are shown, again with most exons marked by RRD (purple marks). (c) Actinomycin-D treatment of male mESCs followed by RNA FISH for Firre over a course of 6 hours. (d) The number of nascent versus mature transcripts counted by image processing in Matlab.

Supplementary Figure 2 Firre is a strictly nuclear lncRNA.

Single molecule RNA fluorescence in situ hybridization (FISH) in HEK293s and HeLa cells, with introns labeled in “green” and exons in “red”, as described in Raj et al. (2008).

Supplementary Figure 3 Firre RNA is sufficient to form ectopic expression domains.

(a) qRT-PCR analysis of the viral overexpression of the human isoform of FIRRE in HEK293, HeLa, and human lung fibroblasts (hLF), and the mouse isoform of Firre in mouse lung fibroblasts (mLF). Normalized to untransduced samples after all CT values are normalized to Gapdh. (b) Single molecule RNA FISH in transduced HeLa and HEK293 cells, which have endogenous Firre expression; introns labeled in “green” and exons in “red”.

Supplementary Figure 4 Firre forms transchromosomal contacts.

(a) Genes that were not detected to be bound by Firre by RAP were used as negative controls for FISH. Firre intron is shown in “green” and Sox2 exons are shown in “red.” (b) RNA co-FISH between the trans targets of Firre: Slc25a12 and Ypel4 (yellow arrows for co-localization): Slc25a12 intron in “green” and Ypel4 intron in “red.”

Supplementary Figure 5 Firre interacts with hnRNPU in mESc and adipose contexts.

(a) The RNA pull-down technique was developed and optimized by testing known lncRNA-protein interactions. For optimization, telomerase RNA TERC was chosen as well as others, such as SRP and 7SK (data not shown). The binding partners of TERC, Dyskerin and TERT, were recovered with high efficiency and specificity. (b) The optimized RNA pull-down technique was used to find the binding partners of Firre. The analysis of mass spectrometry data is outlined. (c) Based on the highest unique peptide counts across different isoforms and lysate conditions, we identified 8 candidate proteins that physically associate with Firre in an RRD-dependent manner. The top candidate was hnRNPU. (d) Firre interacts with hnRNPU in mouse adipose tissue as well as in mESC lysate. Western blots are shown for the pull-downs using in vitro biotinylated isoforms of Firre: five with RRD and one without. We compared end labeling (EL) and body labeling (BL) to exclude the possibility of a bias in binding and used TERC antisense (AS) and sense (S) as negative controls. hnRNPK and A1 are shown for RRD-specific interactions. 20% of the input protein lysate was loaded in the first lane for each Western blot. Input protein lysate and input RNA are included as loading controls.

Supplementary Figure 6 Firre-hnRNPU interaction is biologically relevant, and hnRNPU has a previously shown role in Xist localization.

(a) Endogenous Firre was captured by desthiobiotin-modified DNA oligos in mESCs. The efficiency of capture was measured by qRT-PCR by comparing the RNA levels in the eluate and what is left on the beads post-elution after normalizing to 10% of the total input. The specificity of capture was measured by comparing the eluates from the targeting and scramble oligos. The endogenous RNA pull-down was repeated in mESCs, in which Firre was knocked down to test the specificity of the oligo for the RNA. (b) The endogenous pull-down was repeated in HEK293s to test for the human FIRRE. Additionally, specificity of the oligo was tested by measuring the elutions for the enrichment or depletion of an unrelated lincRNA, linc-Arid4a. (c) Western blot of HEK293 lysates before and after transfection with siRNAs targeting hnRNPU and scramble siRNAs. (d) RNA FISH of Xist in HEK293s after siRNA-mediated depletion of hnRNPU.

Supplementary Figure 7 Uncropped versions of Figure 6a,b.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 (PDF 8212 kb)

Supplementary Table 1

Sequences of Firre transcripts (GenBank KJ638680–KJ638686) In the version of this Table title originally published online, the GenBank accession codes were not included. The information is included as of 10 September 2014. (TXT 28 kb)

Supplementary Table 2

RNA FISH probe sequences (XLSX 58 kb)

Supplementary Table 3

RAP probe sequences (XLSX 29 kb)

Supplementary Table 4

All qRT-PCR primer sequences (XLSX 13 kb)

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Hacisuleyman, E., Goff, L., Trapnell, C. et al. Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat Struct Mol Biol 21, 198–206 (2014). https://doi.org/10.1038/nsmb.2764

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