Skip to main content
Log in

RNA–Chromatin Interactome: What? Where? When?

  • REVIEWS
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract—

It was noticed in the early 1960s that a large amount of RNAs is associated with chromatin. What kind of RNAs are they? Where are they located on chromatin? When and in what processes do these RNAs perform their physiologically normal or pathogenic functions? The review describes the modern approaches that help, to some extent, to answer these questions. Consideration is given to the experimental methods that make it possible to obtain the complete RNA–chromatin interactome of a cell or the genome-wide interaction maps of individual RNAs with chromatin, as well as the methods to process the experimental data. Focus is placed on the noncoding RNAs that function in close contact with chromatin and chromatin-associated protein complexes. A variety of biological examples described using the methods makes it clear that RNAs interacting with chromatin play an important role in the functions of cell systems by finely tuning the chromatin architecture and thus changing the level of gene expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Djebali S., Davis C.A., Merkel A., Dobin A., Lassmann T., Mortazavi A., Tanzer A., Lagarde J., Lin W., Schlesinger F., Xue C., Marinov G.K., Khatun J., Williams B.A., Zaleski C., et al. 2012. Landscape of transcription in human cells. Nature. 489 (7414), 101–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Engreitz J.M., Ollikainen N., Guttman M. 2016. Long non-coding RNAs: Spatial amplifiers that control nuclear structure and gene expression. Nat. Rev. Mol. Cell. Biol. 17, 756–770.

    Article  CAS  PubMed  Google Scholar 

  3. Mishra K., Kanduri C. 2019. Understanding long noncoding RNA and chromatin interactions: What we know so far. Non-Coding RNA. 5 (4), 1–28.

    Article  CAS  Google Scholar 

  4. Engreitz J.M., Pandya-Jones A., McDonel P., Shishkin A., Sirokman K., Surka C., Kadri S., Xing J., Goren A., Lander E.S., Plath K., Guttman M. 2013. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 341 (6147), 1–8.

    Article  CAS  Google Scholar 

  5. Simon M.D., Wang C.I., Kharchenko P.V., West J.A., Chapman B.A., Alekseyenko A.A., Borowsky M.L., Kuroda M.I., Kingston R.E. 2011. The genomic binding sites of a noncoding RNA. Proc. Natl. Acad. Sci. U. S. A. 108 (51), 20497–20502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chu C., Qu K., Zhong F.L., Artandi S.E., Chang H.Y. 2011. Genomic maps of long noncoding RNA occupancy reveal principles of RNA–chromatin interactions. Mol. Cell. 44, 667–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Quinn J.J., Ilik I.A., Qu K., Georgiev P., Chu C., Akhtar A., Chang H.Y. 2014. Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Nat. Biotechnol. 32, 933–940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mondal T., Subhash S., Vaid R., Enroth S., Uday S., Reinius B., Mitra S., Mohammed A., James A.R., Hoberg E., Moustakas A., Gyllensten U., Jones S.J.M., Gustafsson C.M., Sims A.H., et al. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat. Commun. 6 (7743), 1–17.

  9. Chu H.P., Cifuentes-Rojas C., Kesner B., Aeby E., Lee H., Wei C., Oh H.J., Boukhali M., Haas W., Lee J.T. 2017. TERRA RNA antagonizes ATRX and protects telomeres. Cell. 170, 86–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sridhar B., Rivas-Astroza M., Nguyen T.C., Chen W., Yan Z., Cao X., Hebert L., Zhong S. 2017. Systematic mapping of RNA–chromatin interactions in vivo. Curr. Biol. 27, 602–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li X., Zhou B., Chen L., Gou L.T., Li H., Fu X.D. 2017. GRID-seq reveals the global RNA–chromatin interactome. Nat. Biotechnol. 35, 940–950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bell J.C., Jukam D., Teran N.A., Risca V.I., Smith O.K., Johnson W.L., Skotheim J.M., Greenleaf W.J., Straight A.F. 2018. Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA contacts. Elife. 7, 1–28.

    Article  Google Scholar 

  13. Yan Z., Huang N., Wu W., Chen W., Jiang Y., Chen J., Huang X., Wen X., Xu J., Jin Q., Zhang K., Chen Z., Chien S., Zhong S. 2019. Genome-wide colocalization of RNA–DNA interactions and fusion RNA pairs. Proc. Natl. Acad. Sci. U. S. A. 116, 3328–3337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Calandrelli R., Xu L., Luo Y., Wu W., Fan X., Nguyen T., Chen C.-J., Sriram K., Tang X., Burns A.B., Natarajan R., Chen Z.B., Zhong S. 2020. Stress-induced RNA–chromatin interactions promote endothelial dysfunction. Nat. Commun. 11, 1–13.

    Article  CAS  Google Scholar 

  15. Bonetti A., Agostini F., Suzuki A.M., Hashimoto K., Pascarella G., Gimenez J., Roos L., Nash A.J., Ghilotti M., Cameron C.J.F., Valentine M., Medvedeva Y.A., Noguchi S., Agirre E., Kashi K., et al. 2020. RADICL-seq identifies general and cell type-specific principles of genome-wide RNA–chromatin interactions. Nat. Commun. 11, 1–14.

    Article  CAS  Google Scholar 

  16. Gavrilov A.A., Zharikova A.A., Galitsyna A.A., Luzhin A.V., Rubanova N.M., Golov A.K., Petrova N.V., Logacheva M.D., Kantidze O.L., Ulianov S.V., Magnitov M.D., Mironov A.A., Razin S.V. 2020. Studying RNA-DNA interactome by Red-C identifies noncoding RNAs associated with various chromatin types and reveals transcription dynamics. Nucleic Acids Res. 48 (12), 6699–6714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Alfeghaly C., Sanchez A., Rouget R., Thuillier Q., Igel-Bourguignon V., Marchand V., Branlant C., Motorin Y., Behm-Ansmant I., Maenner S. 2021. Implication of repeat insertion domains in the trans-activity of the long non-coding RNA ANRIL. Nucleic Acids Res. 49 (9), 4954–4970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zovoilis A., Cifuentes-Rojas C., Chu H.P., Hernandez A.J., Lee J.T. 2016. Destabilization of B2 RNA by EZH2 activates the stress response. Cell. 167 (7), 1788–1802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Alvarez-Dominguez J.R., Knoll M., Gromatzky A.A., Lodish H.F. 2017. The super-enhancer-derived alncRNA-EC7/bloodlinc potentiates red blood cell development in trans. Cell. Rep. 19 (12), 2503–2514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ballarino M., Cipriano A., Tita R., Santini T., Desideri F., Morlando M., Colantoni A., Carrieri C., Nicoletti C., Musarò A., O’Carroll D., Bozzoni I. 2018. Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice. EMBO J. 37, 1–16.

    Article  CAS  Google Scholar 

  21. Merry C.R., Forrest M.E., Sabers J.N., Beard L., Gao X.-H., Hatzoglou M., Jackson M.W., Wang Z., Markowitz S.D., Khalil A.M. 2015. DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Hum. Mol Genet. 24 (21), 6240–6253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chalei V., Sansom S.N., Kong L., Lee S., Montiel J.F., Vance K.W., Ponting C.P. 2014. The long non-coding RNA Dali is an epigenetic regulator of neural differentiation. Elife. 3, 1–24.

    Article  Google Scholar 

  23. Schmitt A.M., Garcia J.T., Hung T., Flynn R.A., Shen Y., Qu K., Payumo A.Y., Peres-da-Silva A., Broz D.K., Baum R., Guo S., Chen J.K., Attardi L.D., Chang H.Y. 2016. An inducible long noncoding RNA amplifies DNA damage signaling. Nat. Genet. 48 (11), 1370–1376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zapparoli E., Briata P., Rossi M., Brondolo L., Bucci G., Gherzi R. 2020. Comprehensive multi-omics analysis uncovers a group of TGF-β-regulated genes among lncRNA EPR direct transcriptional targets. Nucleic Acids Res. 48 (16), 9053–9066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li M.A., Amaral P.P., Cheung P., Bergmann J.H., Kinoshita M., Kalkan T., Ralser M., Robson S., Meyenn F., Paramor M., Yang F., Chen C., Nichols J., Spector D.L., Kouzarides T., et al. 2017. A lncRNA fine tunes the dynamics of a cell state transition involving lin28, let-7 and de novo DNA methylation. eLife. 6, 1–24.

    Article  Google Scholar 

  26. Hu T., Pi W., Zhu X., Yu M., Ha H., Shi H., Choi J.-H., Tuan D. 2017. Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function. Nucleic Acids Res. 45 (8), 4479–4492.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Luo S., Lu J.Y., Liu L., Yin Y., Chen C., Han X., Wu B., Xu R., Liu W., Yan P., Shao W., Lu Z., Li H., Na J., Tang F., Wang J., Zhang Y.E., Shen X. 2016. Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 18 (5), 637–652.

    Article  CAS  PubMed  Google Scholar 

  28. Hacisuleyman E., Goff L.A., Trapnell C., Williams A., Henao-Mejia J., Sun L., McClanahan P., Hendrickson D.G., Sauvageau M., Kelley D.R., Morse M., Engreitz J., Lander E.S., Guttman M., Lodish H.F., et al. 2019. Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat. Struct. Mol. Biol. 21 (2), 198–206.

    Article  CAS  Google Scholar 

  29. Wang Y., Zhu P., Luo J., Wang J., Liu Z., Wu W., Du Y., Ye B., Wang D., He L., Ren W., Wang J., Sun X., Chen R., Tian Y., Fan Z. 2019. LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling. EMBO J. 38, 1–17.

    Article  Google Scholar 

  30. Yin Y., Yan P., Lu J., Song G., Zhu Y., Li Z., Zhao Y., Shen B., Huang X., Zhu H., Orkin S.H., Shen X. 2015. Opposing roles for the lncRNA haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell. 16, 504–516.

    Article  CAS  PubMed  Google Scholar 

  31. Carlson H.L., Quinn J.J., Yang Y.W., Thornburg C.K., Chang H.Y., Stadler H.S. 2015. LncRNA-HIT functions as an epigenetic regulator of chondrogenesis through its recruitment of p100/CBP complexes. PLoS Genet. 11 (12), 1–30.

    Article  CAS  Google Scholar 

  32. Luo H., Zhu G., Xu J., Lai Q., Yan B., Guo Y., Fung T.K., Zeisig B.B., Cui Y., Zha J., Cogle C., Wang F., Xu B., Yang F.-C., Li W., et al. 2019. HOTTIP lncRNA promotes hematopoietic stem cell self-renewal leading to AML-like disease in mice. Cancer Cell. 36, 645–659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu J., Gao M., He J., Wu K., Lin S., Jin L., Chen Y., Liu H., Shi J., Wang X., Chang L., Lin Y., Zhao Y.-L., Zhang X., Zhang M., et al. 2021. The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature. 591 (7849), 322–326.

    Article  CAS  PubMed  Google Scholar 

  34. Leveille N., Melo C.A., Rooijers K., Dıaz-Lagares A., Melo S.A., Korkmaz G., Lopes R., Moqadam F.A., Maia A.R., Wijchers P.J., Geeven G., den Boer M.L., Kalluri R., de Laat W., Esteller M., Agami R. 2015. Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA. Nat. Commun. 6 (6520), 1–12.

    Article  CAS  Google Scholar 

  35. Lee H.C., Kang D., Han N., Lee Y., Hwang H.J., Lee S.-B., You J.S., Min B.S., Park H.J., Ko Y.-G., Gorospe M., Lee J.-S. 2020. A novel long noncoding RNA Linc-ASEN represses cellular senescence through multileveled reduction of p21 expression. Cell Death Differ. 27 (6), 1844–1861.

    Article  CAS  PubMed  Google Scholar 

  36. Forrest M.E., Saiakhova A., Beard L., Buchner D.A., Scacheri P.C., LaFramboise T., Markowitz S., Khalil A.M. 2018. Colon cancer-upregulated long non-coding RNA lincDUSP regulates cell cycle genes and potentiates resistance to apoptosis. Sci. Rep. 8 (7324), 1–12.

    Article  CAS  Google Scholar 

  37. Ang C.E., Ma Q., Wapinski O.L., Fan S., Flynn R.A., Lee Q.Y., Coe B., Onoguchi M., Olmos V.H., Do B.T., Dukes-Rimsky L., Xu J., Tanabe K., Wang L., Elling U., et al. 2019. The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders. eLife. 8, 1–29.

    Article  Google Scholar 

  38. Luo M., Jeong M., Sun D., Park H.J., Rodriguez B.A.T., Xia Z., Yang L., Zhang X., Sheng K., Darlington G.J., Li W., Goodell M.A. 2015. Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell. 16, 426–438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. West J.A., Davis C.P., Sunwoo H., Simon M.D., Sadreyev R.I., Wang P.I., Tolstorukov M.Y., Kingston R.E. 2014. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Mol. Cell. 55, 791–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Engreitz J.M., Sirokman K., McDonel P., Shishkin A.A., Surka C., Russell P., Grossman S.R., Chow A.Y., Guttman M., Lander E.S. 2014. RNA–RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell. 159, 188–199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yin Y., Lu J.Y., Zhang X., Shao W., Xu Y., Li P., Hong Y., Cui L., Shan G., Tian B., Zhang Q.C., Shen X. 2020. U1 snRNP regulates chromatin retention of noncoding RNAs. Nature. 580 (7801), 147–150.

    Article  CAS  PubMed  Google Scholar 

  42. Iyer S., Modali S.D., Agarwal S.K. 2017. Long noncoding RNA MEG3 is an epigenetic determinant of oncogenic signaling in functional pancreatic neuroendocrine tumor cells. Mol. Cell. Biol. 37 (22), 1–17.

    Article  Google Scholar 

  43. Chakraborty D., Paszkowski-Rogacz M., Berger N., Ding L., Mircetic J., Fu J., Iesmantavicius V., Choudhary C., Anastassiadis K., Stewart A.F., Buchholz F. 2017. lncRNA Panct1 maintains mouse embryonic stem cell identity by regulating TOBF1 recruitment to Oct-Sox sequences in early G1. Cell Rep. 21, 3012–3021.

    Article  CAS  PubMed  Google Scholar 

  44. Chu H.-P., Froberg J.E., Kesner B., Oh H.J., Ji F., Sadreyev R., Pinter S.F., Lee J.T. 2017. PAR-TERRA directs homologous sex chromosome pairing. Nat. Struct. Mol. Biol. 24 (8), 620–631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vance K.W., Sansom S.N., Lee S., Chalei V., Kong L., Cooper S.E., Oliver P.L., Ponting C.P. 2014. The long non-coding RNA Paupar regulates the expression of both local and distal genes. EMBO J. 33 (4), 296–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yang L., Lin C., Jin C., Yang J.C., Tanasa B., Li W., Merkurjev D., Ohgi K.A., Meng D., Zhang J., Evans C.P., Rosenfeld M.G. 2013. LncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature. 500 (7464), 598–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Quinn J.J., Zhang Q.C., Georgiev P., Ilik I.A., Akhtar A., Chang H.Y. 2016. Rapid evolutionary turnover underlies conserved lncRNA–genome interactions. Genes Develop. 30, 191–207.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Fan Z., Chen X., Liu L., Zhu C., Xu J., Yin X., Sheng Y., Zhu Z., Wen L., Zuo X., Zheng X., Zhang Y., Xu J., Huang H., Zhou F., et al. 2020. Association of the polymorphism rs13259960 in SLEAR with predisposition to systemic lupus erythematosus. Arthritis Rheumatol. 72 (6), 985–996.

    Article  CAS  PubMed  Google Scholar 

  49. Wongtrakoongate P., Riddick G., Fucharoen S., Felsenfeld G. 2015. Association of the long non-coding RNA steroid receptor RNA activator (SRA. with TrxG and PRC2 complexes. PLoS Genet. 11 (10), 1–20.

    Article  CAS  Google Scholar 

  50. Sawaengdee W., Cui K., Zhao K., Hongeng S., Fucharoen S., Wongtrakoongate P. 2020. Genome-wide transcriptional regulation of the long non-coding RNA steroid receptor RNA activator in human erythroblasts. Front. Genet. 11 (850), 1–15.

    Article  CAS  Google Scholar 

  51. Marion R.M., Montero J.J., de Silanes I.L., Grana-Castro O., Martınez P., Schoeftner S., Palacios-Fabrega J.A., Blasco M.A. 2019. TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2. eLife. 8, 1–32.

    Article  Google Scholar 

  52. Long J., Badal S.S., Ye Z., Wang Y., Ayanga B.A., Galvan D.L., Green N.H., Chang B.H., Overbeek P.A., Danesh F.R. 2016. Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J. Clin. Invest. 126 (11), 4205–4218.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Simon M.D., Pinter S.F., Fang R., Sarma K., Rutenberg-Schoenberg M., Bowman S.K., Kesner B.A., Maier V.K., Kingston R.E., Lee J.T. 2013. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature. 504 (7480), 465–469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Chen C.-K., Blanco M., Jackson C., Aznauryan E., Ollikainen N., Surka C., Chow A., Cerase A., McDonel P., Guttman M. 2016. Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science. 354 (6311), 468–472.

    Article  CAS  PubMed  Google Scholar 

  55. Wang C.Y., Jégu T., Chu H.P., Oh H.J., Lee L.T. 2018. SMCHD1 merges chromosome compartments and assists formation of super-structures on the inactive X. Cell. 174, 406–421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Colognori D., Sunwoo H., Kriz A.J., Wang C.Y., Lee J.T. 2019. Xist deletional analysis reveals an interdependency between Xist RNA and polycomb complexes for spreading along the inactive X. Mol. Cell. 74, 101–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang C.Y., Colognori D., Sunwoo H., Wang D., Lee J.T. 2019. PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments. Nat. Commun. 10 (2950), 1–18.

    CAS  Google Scholar 

  58. Pandya-Jones A., Markaki Y., Serizay J., Chitiashvili T., Leon W.R.M., Damianov A., Chronis C., Papp B., Chen C.-K., McKee R., Wang X.-J., Chau A., Sabri S., Leonhardt H., Zheng S., Guttman M., et al. 2020. A protein assembly mediates Xist localization and gene silencing. Nature. 587 (7832), 145–151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Powell W.T., Coulson R.L., Crary F.K., Wong S.S., Ach R.A., Tsang P., Yamada N.A., Yasui D.H., LaSalle J.M. 2013. A Prader–Willi locus lncRNA cloud modulates diurnal genes and energy expenditure. Hum. Mol. Genet. 22 (21), 4318–4328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu W., Ma Q., Wong K., Li W., Ohgi K., Zhang J., Aggarwal A.K., Rosenfeld M.G. 2013. Brd4 and JMJD6-associated anti-pause enhancers in regulation of transcriptional pause release. Cell. 155, 1581–1595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Flynn R.A., Do B.T., Rubin A.J., Calo E., Lee B., Kuchelmeister H., Rale M., Chu C., Kool E.T., Wysocka J., Khavari P.A., Chang H.Y. 2016. 7SK-BAF axis controls pervasive transcription at enhancers. Nat. Struct. Mol. Biol. 23 (3), 231–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Studniarek C., Tellier M., Martin P.G.P., Murphy S., Kiss T., Egloff S. 2021. The 7SK/P-TEFb snRNP controls ultraviolet radiation-induced transcriptional reprogramming. Cell Rep. 35 (2), 1–14.

    Article  CAS  Google Scholar 

  63. Pandey R.R., Mondal T., Mohammad F., Enroth S., Redrup L., Komorowski J., Nagano T., Mancini-DiNardo D., Kanduri C. 2008. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell. 32, 232–246.

    Article  CAS  PubMed  Google Scholar 

  64. Man H.S.J., Sukumar A.N., Lam G.C., Turgeon P.J., Yan M.S., Ku K.H., Dubinsky M.K., Ho J.J.D., Wang J.J., Das S., Mitchell N., Oettgen P., Sefton M.V., Marsden P.A. 2018. Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc. Natl. Acad. Sci. U. S. A. 115 (10), 2401–2406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Colak D., Zaninovic N., Cohen M.S., Rosenwaks Z., Yang W.-Y., Gerhardt J., Disney M.D., Jaffrey S.R. 2014. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science. 343 (6174), 1002–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhang Y., Liu T., Meyer C.A., Eeckhoute J., Johnson D.S., Bernstein B.E., Nusbaum C., Myers R.M., Brown M., Li W., Liu X.S. 2008. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9 (9), 1–9.

    Article  Google Scholar 

  67. Xu S., Grullon S., Ge K., Peng W. 2014. Spatial clustering for identification of ChIP-enriched regions (SICER) to Map regions of histone methylation patterns in embryonic stem cells. Methods in Molecular Biology (Methods and Protocols). 1150, 97–111.

    Article  CAS  PubMed  Google Scholar 

  68. Heinz S., Benner C., Spann N., Bertolino E., Lin Y.C., Laslo P., Cheng J.X., Murre C., Singh H., Glass C.K. 2010. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell. 38, 576–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kharchenko P.V., Tolstorukov M.Y., Park P.J. 2008. Design and analysis of ChIP-seq experiments for DNA-binding proteins. Nat. Biotechnol. 26 (12), 1351–1359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rice P., Longden L., Bleasby A. 2000. EMBOSS: The European molecular biology open software suite. Trends Genet. 16 (6), 276–277.

    Article  CAS  PubMed  Google Scholar 

  71. Buske F.A., Bauer D.C., Mattick J.S., Bailey T.L. 2012. Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data. Genome Res. 22, 1372–1381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kuo C.-C., Hanzelmann S., Cetin N.S., Frank S., Zajzon B., Derks J.-P., Akhade V.S., Ahuja G., Kanduri C., Grummt I., Kurian L., Costa I.G. 2019. Detection of RNA–DNA binding sites in long noncoding RNAs. Nucleic Acids Res. 47 (6), 1–12.

    Article  CAS  Google Scholar 

  73. Matveishina E., Antonov I., Medvedeva Y.A. 2020. Practical guidance in genome-wide RNA:DNA triple helix prediction. Int. J. Mol. Sci. 21 (830), 1–12.

    Article  CAS  Google Scholar 

  74. Bailey T.L., Johnson J., Grant C.E., Noble W.S. 2015. The MEME suite. Nucleic Acids Res. 43, 39–49.

    Article  CAS  Google Scholar 

  75. Gupta S., Stamatoyannopoulos J.A., Bailey T.L., Noble W.S. 2007. Quantifying similarity between motifs. Genome Biol. 8, 1–9.

    Article  CAS  Google Scholar 

  76. Martianov I., Ramadass A., Barros A.S., Chow N., Akoulitchev A. 2007. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature. 445 (7128), 666–670.

    Article  CAS  PubMed  Google Scholar 

  77. Khomyakova E.B., Gousset H., Liquier J., Huynh-Dinh T., Gouyette C., Takahashi M., Florentiev V.L., Taillandier E. 2000. Parallel intramolecular DNA triple helix with G and T bases in the third strand stabilized by Zn2+ ions. Nucleic Acids Res. 28 (18), 3511–3516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Besch R., Giovannangeli C., Kammerbauer C., Degitz K. 2002. Specific inhibition of ICAM-1 expression mediated by gene targeting with triplex-forming oligonucleotides. J. Biol. Chem. 277 (36), 32473–32479.

    Article  CAS  PubMed  Google Scholar 

  79. McLean C.Y., Bristor D., Hiller M., Clarke S.L., Schaar B.T., Lowe C.B., Wenger A.M., Bejerano G. 2010. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28 (5), 495–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shin H., Liu T., Manrai A.K., Liu S.X. 2009. CEAS: cis-regulatory element annotation system. Bioinformatics. 25 (19), 2605–2606.

    Article  CAS  PubMed  Google Scholar 

  81. Mi H., Muruganujan A., Ebert D., Huang X., Thomas P.D. 2019. PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 47, 419–426.

    Article  CAS  Google Scholar 

  82. Huang D.W., Sherman B.T., Lempicki R.A. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protocols. 4 (1), 44–57.

    Article  CAS  Google Scholar 

  83. Binns D., Dimmer E., Huntley R., Barrell D., O’Donovan C., Apweiler R. 2009. QuickGO: A web-based tool for Gene Ontology searching. Proteomics. 25 (22), 3045–3046.

    CAS  Google Scholar 

  84. Kuleshov M.V., Jones M.R., Rouillard A.D., Fernandez N.F., Duan Q., Wang Z., Koplev S., Jenkins S.L., Jagodnik K.M., Lachmann A., McDermott M.G., Monteiro C.D., Gundersen G.W., Ma’ayan A. 2016. Enrichr: A comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, 90–97.

    Article  CAS  Google Scholar 

  85. Chodroff R.A., Goodstadt L., Sirey T.M., Oliver P.L., Davies K.E., Green E.D., Molnár Z., Ponting C.P. 2010. Long noncoding RNA genes: Conservation of sequence and brain expression among diverse amniotes. Genome Biol. 11 (7), 1–16.

    Article  CAS  Google Scholar 

  86. Ulitsky I., Shkumatava A., Jan C.H., Sive H., Bartel D.P. 2011. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell. 147 (7), 1537–1550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Gelbart M.E., Kuroda M.I. 2009. Drosophila dosage compensation: A complex voyage to the X chromosome. Development, 136 (9), 1399–1410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Larschan E., Bishop E.P., Kharchenko P.V., Core L.J., Lis J.T., Park P.J., Kuroda M.I. 2011. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila. Nature. 471 (7336), 115–118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Meller V.H., Rattner B.P. 2002. The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex. EMBO J. 21 (5), 1084–1091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Disteche C.M. 2012. Dosage compensation of the sex chromosomes. Annu. Rev. Genet. 46, 537–560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lee J.T. 2012. Epigenetic regulation by long noncoding RNAs. Science. 338 (6113), 1435–1439.

  92. Wutz A. 2011. Gene silencing in X-chromosome inactivation: Advances in understanding facultative heterochromatin formation. Nat. Rev. Genet. 12(8), 542–553.

    Article  CAS  PubMed  Google Scholar 

  93. Giorgetti L., Lajoie B.R., Carter A.C., Attia M., Zhan Y., Xu J., Chen C.J., Kaplan N., Chang H.Y., Heard E., Dekker J. 2016. Structural organization of the inactive X chromosome in the mouse. Nature. 535 (7613), 575–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Splinter E., de Wit E., Nora E.P., Klous P., van de Werken H.J.G., Zhu Y., Kaaij L.J.T., van IJcken W., Gribnau J., Heard E., de Laat W. 2011. The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes Dev. 25 (13), 1371–1383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Minajigi A., Froberg J.E., Wei C., Sunwoo H., Kesner B., Colognori D., Lessing D., Payer B., Boukhali M., Haas W., Lee J.T. 2015. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science. 349 (6245), 1–10.

    Article  CAS  Google Scholar 

  96. Schoeftner S., Sengupta A.K., Kubicek S., Mechtler K., Spahn L., Koseki H., Jenuwein T., Wutz A. 2006. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25 (13), 3110–3122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Zhao J., Sun B.K., Erwin J.A., Song J.J., Lee J.T. 2008. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 322 (5902), 750–756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chu C., Zhang Q.C., da Rocha S.T., Flynn R.A., Bharadwaj M., Calabrese J.M., Magnuson T., Heard E., Chang H.Y. 2015. Systematic discovery of Xist RNA binding proteins. Cell. 161 (2), 404–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Brockdorff N. 2018. Local tandem repeat expansion in Xist RNA as a model for the functionalisation of ncRNA. Non-Coding RNA. 4(4), 1–11.

    Article  CAS  Google Scholar 

  100. McHugh C.A., Chen C.-K., Chow A., Surka C.F., Tran C., McDonel P., Pandya-Jones A., Blanco M., Burghard C., Moradian A., Sweredoski M.J., Shishkin A.A., Su J., Lander E.S., Hess S., et a. 2015. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature. 521 (7551), 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Hutchinson J.H., Ensminger A.W., Clemson C.M., Lynch C.R., Lawrence J.B., Chess A. 2007. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics. 8 (39), 1–16.

    Article  CAS  Google Scholar 

  102. Zhang X., Hamblin M.H., Yin K.J. 2017. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 14 (12), 1705–1714.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Clemson C.M., Hutchinson J.N., Sara S.A., Ensminger A.W., Fox A.H., Chess A., Lawrence J.B. 2009. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol. Cell. 33 (6), 717–726.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Imamura K., Imamachi N., Akizuki G., Kumakura M., Kawaguchi A., Nagata K., Kato A., Kawaguchi Y., Sato H., Yoneda M., Kai C., Yada T., Suzuki Y., Yamada T., Ozawa T., et al. 2014. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Mol. Cell. 53 (3), 393–406.

    Article  CAS  PubMed  Google Scholar 

  105. Hirose T., Virnicchi G., Tanigawa A., Naganuma T., Li R., Kimura H., Yokoi T., Nakagawa S., Bénard M., Fox A.H., Pierron G. 2014. NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol. Biol. Cell. 25, 169–183.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Kaida D., Berg M.G., Younis I., Kasim M., Singh L.N., Wan L., Dreyfuss G. 2010. U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation. Nature. 468 (7324), 664–668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gupta R.A., Shah N., Wang K.C., Kim J., Horlings H.M., Wong D.J., Tsai M.-C., Hung T., Argani P., Rinn J.L., Wang Y., Brzoska P., Kong B., Li R., West R.B., van de Vijver M.J., Sukumar S., Chang H.Yet al. 2010. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464 (7291), 1071–1076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Rinn J.L., Kertesz M., Wang J.K., Squazzo S.L., Xu X., Brugmann S.A., Goodnough H., Helms J.A., Farnham P.J., Segal E., Chang H.Y. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 129 (7), 1311–1323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tsai M.-C., Manor O., Wan Y., Mosammaparast N., Wang J.K., Lan F., Shi Y., Segal E., Chang H.Y. 2010. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 329 (5992), 689–693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ernst J., Kheradpour P., Mikkelsen T.S., Shoresh N., Ward L.D., Epstein C.B., Zhang X., Wang L., Issner R., Coyne M., Ku M., Durham T., Kellis M., Bernstein B.E. 2011. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 473 (7345), 43–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Laurent G.S., Shtokalo D., Dong B., Tackett M.R., Fan X., Lazorthes S., Nicolas E., Sang N., Triche T.J., McCaffrey T.A., Xiao W., Kapranov P. 2013. VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biol. 14, 1–20.

    Article  CAS  Google Scholar 

  112. Wang Y., Hu S.-B., Wang M.-R., Yao R.-W., Wu D., Yang L., Chen L.-L. 2018. Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria. Nat. Cell Biol. 20 (10), 1145–1158.

    Article  CAS  PubMed  Google Scholar 

  113. Binder S., Hösler N., Riedel D., Zipfel I., Buschmann T., Kämpf C., Reiche K., Burger R., Gramatzki M., Hackermüller J., Stadler P.F., Horn F. 2017. STAT3-induced long noncoding RNAs in multiple myeloma cells display different properties in cancer. Sci. Rep. 7 (7976), 1–13.

    Article  CAS  Google Scholar 

  114. Guh C.Y., Hsieh Y.H., Chu H.P. 2020. Functions and properties of nuclear lncRNAs-from systematically mapping the interactomes of lncRNAs. J. Biomed. Sci. 27 (44), 1–14.

    Article  CAS  Google Scholar 

  115. Cetin N.S., Kuo C.C., Ribarska T., Li R., Costa I.G., Grummt I. 2019. Isolation and genome-wide characterization of cellular DNA:RNA triplex structures. Nucleic Acids Res. 47 (5), 2306–2321

    Article  CAS  Google Scholar 

  116. Rom A., Melamed L., Gil N., Goldrich M.J., Kadir R., Golan M., Biton I., Perry R.B.-T., Ulitsky I. 2019. Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability. Nat. Commun. 10 (5092), 1–15.

    Article  CAS  Google Scholar 

  117. Zhang G., Lan Y., Xie A., Shi J., Zhao H., Xu L., Zhu S., Luo T., Zhao T., Xiao Y., Li X. 2019. Comprehensive analysis of long noncoding RNA (lncRNA)—chromatin interactions reveals lncRNA functions dependent on binding diverse regulatory elements. J. Biol. Chem. 294 (43), 15613–15622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 20-04-00459 A).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G. K. Ryabykh.

Ethics declarations

Conflict of interests. The authors declare that they have no conflict of interest.

This work does not contain any studies involving animals or human subjects performed by any of the authors.

Additional information

Translated by T. Tkacheva

Abbreviations: all-to-all methods (MARGI, GRID-seq, ChAR-seq, iMARGI, RADICL-seq, and Red-C), methods that report all potential RNA–chromatin interactions in the cell; ncRNA, noncoding RNA; one-to-all methods (RAP, CHART-seq, ChIRP-seq, dChIRP-seq, ChOP-seq, and CHIRT-seq), methods that report the binding sites of a particular RNA throughout the genome; peak, a genome region enriched in contacts of a particular RNA with chromatin; TAD, topologically associated domain; chRNA, chromatin-associated RNA; chDNA, chromatin DNA; ESC, embryonic stem cell; input, data with background nonspecific contacts; GO, gene ontology; X-RNA, early unknown chRNA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ryabykh, G.K., Mylarshchikov, D.E., Kuznetsov, S.V. et al. RNA–Chromatin Interactome: What? Where? When?. Mol Biol 56, 210–228 (2022). https://doi.org/10.1134/S0026893322020121

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893322020121

Keywords:

Navigation