Skip to main content
SpringerLink
Log in

Regulation of epigenetic processes by non-coding RNAs

  • Review Article
  • Published:
The Nucleus Aims and scope Submit manuscript

Abstract

Non-coding RNAs (ncRNAs) have emerged as important regulators of a variety of cellular mechanisms, including chromatin organization. Many ncRNAs play an integral role in modifying chromatin structure by recruiting and directing chromatin-modifying protein complexes to target genomic loci. A subset of ncRNAs is also involved in recruiting chromatin-modifying complexes that impart stable epigenetic marks onto the chromatin, which are propagated through cell divisions and/or generations. The placement of these epigenetic marks by ncRNAs leads to changes in chromatin structure and organization, which affects the accessibility of DNA by transcription factors, leading to the activation or repression of the transcription of target DNA loci. Here, we discuss the role of ncRNAs in various epigenetic processes such as the maintenance and formation of pericentric heterochromatin in both S. pombe and mammals, dosage compensation in both Drosophila and mammals, transgenerational epigenetic inheritance in which small interfering RNAs lead to stable gene silencing that is propagated to future generations in C. elegans, and finally, centromere inheritance.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Akkouche A, Mugat B, Barckmann B, Varela-Chavez C, Li B, Raffel R, et al. Piwi Is required during Drosophila embryogenesis to license dual-strand piRNA clusters for transposon repression in adult ovaries. Mol Cell. 2017;66:411-9.e4.

    Article  CAS  PubMed  Google Scholar 

  2. Allshire RC, Ekwall K. Epigenetic regulation of chromatin states in Schizosaccharomyces pombe. Cold Spring Harb Perspect Biol. 2015;7:a018770.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Alper BJ, Lowe BR, Partridge JF. Centromeric heterochromatin assembly in fission yeast–balancing transcription, RNA interference and chromatin modification. Chromosome Res. 2012;20:521–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Andersen PR, Tirian L, Vunjak M, Brennecke J. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature. 2017;549:54–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anguera MC, Sun BK, Xu N, Lee JT. X-chromosome kiss and tell: how the Xs go their separate ways. Cold Spring Harb Symp Quant Biol. 2006;71:429–37.

    Article  CAS  PubMed  Google Scholar 

  6. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barnhart MC, Kuich PH, Stellfox ME, Ward JA, Bassett EA, Black BE, et al. HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. J Cell Biol. 2011;194:229–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Becker JS, Nicetto D, Zaret KS. H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet. 2016;32:29–41.

    Article  CAS  PubMed  Google Scholar 

  9. Beletskii A, Hong YK, Pehrson J, Egholm M, Strauss WM. PNA interference mapping demonstrates functional domains in the noncoding RNA Xist. Proc Natl Acad Sci U S A. 2001;98:9215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Belote JM, Lucchesi JC. Male-specific lethal mutations of Drosophila melanogaster. Genetics. 1980;96:165–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bernstein E, Allis CD. RNA meets chromatin. Genes Dev. 2005;19:1635–55.

    Article  CAS  PubMed  Google Scholar 

  12. Black BE, Cleveland DW. Epigenetic centromere propagation and the nature of CENP-a nucleosomes. Cell. 2011;144:471–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Böhmdorfer G, Wierzbicki AT. Control of chromatin structure by long noncoding RNA. Trends Cell Biol. 2015;25:623–32.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bond CS, Fox AH. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009;186:637–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 2007;128:1089–103.

    Article  CAS  PubMed  Google Scholar 

  16. Brockdorff N. Localized accumulation of Xist RNA in X chromosome inactivation. Open Biol. 2019;9:190213.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brockdorff N. Polycomb complexes in X chromosome inactivation. Philos Trans R Soc Lond B Biol Sci. 2017;372:20170021.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, et al. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992;71:515–26.

    Article  CAS  PubMed  Google Scholar 

  19. Brockdorff N, Turner BM. Dosage compensation in mammals. Cold Spring Harb Perspect Biol. 2015;7:a019406.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71:527–42.

    Article  CAS  PubMed  Google Scholar 

  21. Buker SM, Iida T, Bühler M, Villén J, Gygi SP, Nakayama J, et al. Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast. Nat Struct Mol Biol. 2007;14:200–7.

    Article  CAS  PubMed  Google Scholar 

  22. Cam HP, Sugiyama T, Chen ES, Chen X, FitzGerald PC, Grewal SI. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat Genet. 2005;37:809–19.

    Article  CAS  PubMed  Google Scholar 

  23. Casanova M, Pasternak M, El Marjou F, Le Baccon P, Probst AV, Almouzni G. Heterochromatin reorganization during early mouse development requires a single-stranded noncoding transcript. Cell Rep. 2013;4:1156–67.

    Article  CAS  PubMed  Google Scholar 

  24. Cerase A, Pintacuda G, Tattermusch A, Avner P. Xist localization and function: new insights from multiple levels. Genome Biol. 2015;16:166.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chadwick BP, Valley CM, Willard HF. Histone variant macroH2A contains two distinct macrochromatin domains capable of directing macroH2A to the inactive X chromosome. Nucleic Acids Res. 2001;29:2699–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chan FL, Marshall OJ, Saffery R, Kim BW, Earle E, Choo KH, et al. Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proc Natl Acad Sci USA. 2012;109:1979–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chujo T, Hirose T. Nuclear bodies built on architectural long noncoding RNAs: unifying principles of their construction and function. Mol Cells. 2017;40:889–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chujo T, Yamazaki T, Hirose T. Architectural RNAs (arcRNAs): a class of long noncoding RNAs that function as the scaffold of nuclear bodies. Biochim Biophys Acta. 2016;1859:139–46.

    Article  CAS  PubMed  Google Scholar 

  29. Cohen A, Habib A, Laor D, Yadav S, Kupiec M, Weisman R. TOR complex 2 in fission yeast is required for chromatin-mediated gene silencing and assembly of heterochromatic domains at subtelomeres. J Biol Chem. 2018;293:8138–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cohen AL, Jia S. Noncoding RNAs and the borders of heterochromatin. Wiley Interdiscip Rev RNA. 2014;5:835–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Creamer KM, Lawrence JB. RNA: a window into the broader role of RNA in nuclear chromosome architecture. Philos Trans R Soc Lond B Biol Sci. 2017;372:20160360.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Cutter DiPiazza AR, Taneja N, Dhakshnamoorthy J, Wheeler D, Holla S, Grewal SIS. Spreading and epigenetic inheritance of heterochromatin require a critical density of histone H3 lysine 9 tri-methylation. PNAS. 2021;118:e2100699118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dai Z, Ramesh V, Locasale JW. The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet. 2020;21:737–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Disteche CM, Berletch JB. X-chromosome inactivation and escape. J Genet. 2015;94:591–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Du Y, Topp CN, Dawe RK. DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA. PLoS Genet. 2010;6:e1000835.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Eymery A, Horard B, El Atifi-Borel M, Fourel G, Berger F, Vitte AL, et al. A transcriptomic analysis of human centromeric and pericentric sequences in normal and tumor cells. Nucleic Acids Res. 2009;37:6340–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fabrizio P, Garvis S, Palladino F. Histone methylation and memory of environmental stress. Cells. 2019;8:339.

    Article  CAS  PubMed Central  Google Scholar 

  38. Fagegaltier D, Bougé AL, Berry B, Poisot E, Sismeiro O, Coppée JY, et al. The endogenous siRNA pathway is involved in heterochromatin formation in Drosophila. Proc Natl Acad Sci U S A. 2009;106:21258–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Filippova GN, Cheng MK, Moore JM, Truong JP, Hu YJ, Nguyen DK, et al. Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development. Dev Cell. 2005;8:31–42.

    Article  CAS  PubMed  Google Scholar 

  40. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806–11.

    Article  CAS  PubMed  Google Scholar 

  41. Friedrich T, Faivre L, Bäurle I, Schubert D. Chromatin-based mechanisms of temperature memory in plants. Plant Cell Environ. 2019;42:762–70.

    Article  CAS  PubMed  Google Scholar 

  42. Garrido-Ramos MA. Satellite DNA: an evolving topic. Genes (Basel). 2017;8:230.

    Article  Google Scholar 

  43. Gelbart ME, Larschan E, Peng S, Park PJ, Kuroda MI. Drosophila MSL complex globally acetylates H4K16 on the male X chromosome for dosage compensation. Nat Struct Mol Biol. 2009;16:825–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gilbert N, Boyle S, Fiegler H, Woodfine K, Carter NP, Bickmore WA. Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell. 2004;118:555–66.

    Article  CAS  PubMed  Google Scholar 

  45. Greer EL, Beese-Sims SE, Brookes E, Spadafora R, Zhu Y, Rothbart SB, et al. A histone methylation network regulates transgenerational epigenetic memory in C. elegans. Cell Rep. 2014;7:113–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Greer EL, Maures TJ, Hauswirth AG, Green EM, Leeman DS, Maro GS, et al. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature. 2010;466:383–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature. 2011;479:365–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Grewal SI, Rice JC. Regulation of heterochromatin by histone methylation and small RNAs. Curr Opin Cell Biol. 2004;16:230–8.

    Article  CAS  PubMed  Google Scholar 

  49. Guenatri M, Bailly D, Maison C, Almouzni G. Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol. 2004;166:493–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hall IM, Shankaranarayana GD, Noma K, Ayoub N, Cohen A, Grewal SI. Establishment and maintenance of a heterochromatin domain. Science. 2002;297:2232–7.

    Article  CAS  PubMed  Google Scholar 

  51. Helbig R, Fackelmayer FO. Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain. Chromosoma. 2003;112:173–82.

    Article  CAS  PubMed  Google Scholar 

  52. Huo X, Ji L, Zhang Y, Lv P, Cao X, Wang Q, et al. The nuclear matrix protein SAFB cooperates with major satellite RNAs to stabilize heterochromatin architecture partially through phase separation. Mol Cell. 2020;77:368-83.e7.

    Article  CAS  PubMed  Google Scholar 

  53. Ideue T, Tani T. Centromeric non-coding RNAs: conservation and diversity in function. Noncoding RNA. 2020;6:4.

    Article  CAS  PubMed Central  Google Scholar 

  54. Ilik IA, Quinn JJ, Georgiev P, Tavares-Cadete F, Maticzka D, Toscano S, et al. Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Mol Cell. 2013;51:156–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Janssen A, Colmenares SU, Karpen GH. Heterochromatin: guardian of the genome. Annu Rev Cell Dev Biol. 2018;34:265–88.

    Article  CAS  PubMed  Google Scholar 

  56. Johnson WL, Yewdell WT, Bell JC, McNulty SM, Duda Z, O’Neill RJ, et al. RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. Elife. 2017. https://doi.org/10.7554/eLife.25299.

  57. Jolly C, Metz A, Govin J, Vigneron M, Turner BM, Khochbin S, et al. Stress-induced transcription of satellite III repeats. J Cell Biol. 2004;164:25–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011;90:430–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kalinava N, Ni JZ, Gajic Z, Kim M, Ushakov H, Gu SGC. elegans heterochromatin factor SET-32 plays an essential role in transgenerational establishment of nuclear RNAi-mediated epigenetic silencing. Cell Rep. 2018;25:2273-84.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kelley RL, Kuroda MI. The drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male-specific lethal dosage compensation complex. Genetics. 2003;164:565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Keverne EB. Significance of epigenetics for understanding brain development, brain evolution and behaviour. Neuroscience. 2014;264:207–17.

    Article  CAS  PubMed  Google Scholar 

  62. Kixmoeller K, Allu PK, Black BE. The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle. Open Biol. 2020;10:200051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Klosin A, Casas E, Hidalgo-Carcedo C, Vavouri T, Lehner B. Transgenerational transmission of environmental information in. Science. 2017;356:320–3.

    Article  CAS  PubMed  Google Scholar 

  64. Kung JT, Kesner B, An JY, Ahn JY, Cifuentes-Rojas C, Colognori D, et al. Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Mol Cell. 2015;57:361–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lakhotia SC. Non-coding RNAs demystify constitutive heterochromatin as essential modulator of epigenotype. Nucleus. 2017;60:299–314.

    Article  Google Scholar 

  66. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017;547:236–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  CAS  PubMed  Google Scholar 

  68. Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13:1192–200.

    Article  CAS  PubMed  Google Scholar 

  69. Lekka E, Hall J. Noncoding RNAs in disease. FEBS Lett. 2018;592:2884–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lev I, Gingold H, Rechavi O. H3K9me3 is required for inheritance of small RNAs that target a unique subset of newly evolved genes. Elife. 2019. https://doi.org/10.7554/eLife.40448.

  71. Lev I, Seroussi U, Gingold H, Bril R, Anava S, Rechavi O. MET-2-dependent H3K9 methylation suppresses transgenerational small RNA inheritance. Curr Biol. 2017;27:1138–47.

    Article  CAS  PubMed  Google Scholar 

  72. Lewandowski JP, Lee JC, Hwang T, Sunwoo H, Goldstein JM, Groff AF, et al. The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis. Nat Commun. 2019;10:5137.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lu J, Gilbert DM. Proliferation-dependent and cell cycle regulated transcription of mouse pericentric heterochromatin. J Cell Biol. 2007;179:411–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lucchesi JC, Kuroda MI. Dosage compensation in Drosophila. Cold Spring Harb Perspect Biol. 2015;7:a019398.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Lv M, Yao Y, Li F, Xu L, Yang L, Gong Q, et al. Structural insights reveal the specific recognition of roX RNA by the dsRNA-binding domains of the RNA helicase MLE and its indispensable role in dosage compensation in Drosophila. Nucleic Acids Res. 2019;47:3142–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 2010;11:285–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Marmorstein R, Trievel RC. Histone modifying enzymes: structures, mechanisms, and specificities. Biochim Biophys Acta. 2009;1789:58–68.

    Article  CAS  PubMed  Google Scholar 

  78. Martienssen R, Moazed D. RNAi and heterochromatin assembly. Cold Spring Harb Perspect Biol. 2015;7:a019323.

    Article  PubMed  PubMed Central  Google Scholar 

  79. McMurchy AN, Stempor P, Gaarenstroom T, Wysolmerski B, Dong Y, Aussianikava D, et al. A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress. Elife. 2017. https://doi.org/10.7554/eLife.32516.

  80. McNulty SM, Sullivan LL, Sullivan BA. Human centromeres produce chromosome-specific and array-specific alpha satellite transcripts that are complexed with CENP-A and CENP-C. Dev Cell. 2017;42:226-40.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Meller VH, Joshi SS, Deshpande N. Modulation of chromatin by noncoding RNA. Annu Rev Genet. 2015;49:673–95.

    Article  CAS  PubMed  Google Scholar 

  82. Mermoud JE, Costanzi C, Pehrson JR, Brockdorff N. Histone macroH2A1.2 relocates to the inactive X chromosome after initiation and propagation of X-inactivation. J Cell Biol. 1999;147:1399–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38:23–38.

    Article  CAS  PubMed  Google Scholar 

  84. Morales V, Straub T, Neumann MF, Mengus G, Akhtar A, Becker PB. Functional integration of the histone acetyltransferase MOF into the dosage compensation complex. EMBO J. 2004;23:2258–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Muchardt C, Guilleme M, Seeler JS, Trouche D, Dejean A, Yaniv M. Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1alpha. EMBO Rep. 2002;3:975–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Nakama M, Kawakami K, Kajitani T, Urano T, Murakami Y. DNA-RNA hybrid formation mediates RNAi-directed heterochromatin formation. Genes Cells. 2012;17:218–33.

    Article  CAS  PubMed  Google Scholar 

  87. Nambiar M, Smith GR. Pericentromere-Specific Cohesin Complex Prevents Meiotic Pericentric DNA Double-Strand Breaks and Lethal Crossovers. Mol Cell. 2018;71:540-53.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Narlikar GJ. Phase-separation in chromatin organization. J Biosci. 2020. https://doi.org/10.1007/s12038-019-9978-z.

  89. Nesterova TB, Slobodyanyuk SY, Elisaphenko EA, Shevchenko AI, Johnston C, Pavlova ME, et al. Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Res. 2001;11:833–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Neumann P, Yan H, Jiang J. The centromeric retrotransposons of rice are transcribed and differentially processed by RNA interference. Genetics. 2007;176:749–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Nicetto D, Zaret KS. Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev. 2019;55:1–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Nishibuchi G, Déjardin J. The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals. Chromosome Res. 2017;25:77–87.

    Article  CAS  PubMed  Google Scholar 

  93. Noa A, Kuan HS, Aschmann V, Zaburdaev V, Hilbert L. The hierarchical packing of euchromatin domains can be described as multiplicative cascades. PLoS Comput Biol. 2021;17:e1008974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Nozawa RS, Nagao K, Igami KT, Shibata S, Shirai N, Nozaki N, et al. Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HBiX1 pathway. Nat Struct Mol Biol. 2013;20:566–73.

    Article  CAS  PubMed  Google Scholar 

  95. Pacini G, Dunkel I, Mages N, Mutzel V, Timmermann B, Marsico A, et al. Integrated analysis of Xist upregulation and X-chromosome inactivation with single-cell and single-allele resolution. Nat Commun. 2021;12:3638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Penagos-Puig A, Furlan-Magaril M. Heterochromatin as an important driver of genome organization. Front Cell Dev Biol. 2020;8:579137.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Perea-Resa C, Blower MD. Centromere biology: transcription goes on stage. Mol Cell Biol. 2018;38:e00263-e318.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Perez MF, Lehner B. Intergenerational and transgenerational epigenetic inheritance in animals. Nat Cell Biol. 2019;21:143–51.

    Article  CAS  PubMed  Google Scholar 

  99. Petrie VJ, Wuitschick JD, Givens CD, Kosinski AM, Partridge JF. RNA interference (RNAi)-dependent and RNAi-independent association of the Chp1 chromodomain protein with distinct heterochromatic loci in fission yeast. Mol Cell Biol. 2005;25:2331–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Phillips JE, Corces VG. CTCF: master weaver of the genome. Cell. 2009;137:1194–211.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Pintacuda G, Young AN, Cerase A. Function by structure: spotlights on Xist long non-coding RNA. Front Mol Biosci. 2017;4:90.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Prothero KE, Stahl JM, Carrel L. Dosage compensation and gene expression on the mammalian X chromosome: one plus one does not always equal two. Chromosome Res. 2009;17:637–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Quénet D, Dalal Y. A long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife. 2014;3:e03254.

    Article  PubMed  Google Scholar 

  104. Ragunathan K, Jih G, Moazed D. Epigenetic inheritance uncoupled from sequence-specific recruitment. Science. 2015;348:1258699.

    Article  PubMed  Google Scholar 

  105. Rechavi O, Houri-Ze’evi L, Anava S, Goh WSS, Kerk SY, Hannon GJ, et al. Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell. 2014;158:277–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Rechavi O, Lev I. Principles of transgenerational Small RNA inheritance in caenorhabditis elegans. Curr Biol. 2017;27:R720–30.

    Article  CAS  PubMed  Google Scholar 

  107. Rechavi O, Minevich G, Hobert O. Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell. 2011;147:1248–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901–6.

    Article  CAS  PubMed  Google Scholar 

  109. Richards EJ, Elgin SC. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell. 2002;108:489–500.

    Article  CAS  PubMed  Google Scholar 

  110. Rieder CL. Ribonucleoprotein staining of centrioles and kinetochores in newt lung cell spindles. J Cell Biol. 1979;80:1–9.

    Article  CAS  PubMed  Google Scholar 

  111. Rizzi N, Denegri M, Chiodi I, Corioni M, Valgardsdottir R, Cobianchi F, et al. Transcriptional activation of a constitutive heterochromatic domain of the human genome in response to heat shock. Mol Biol Cell. 2004;15:543–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Rošić S, Köhler F, Erhardt S. Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. J Cell Biol. 2014;207:335–49.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Ruby JG, Jan C, Player C, Axtell MJ, Lee W, Nusbaum C, et al. Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell. 2006;127:1193–207.

    Article  CAS  PubMed  Google Scholar 

  114. Sahakyan A, Yang Y, Plath K. The role of Xist in X-chromosome dosage compensation. Trends Cell Biol. 2018;28:999–1013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, et al. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev. 2006;20:2214–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Saksouk N, Simboeck E, Déjardin J. Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin. 2015;8:3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Samata M, Akhtar A. Dosage compensation of the X chromosome: a complex epigenetic assignment involving chromatin regulators and long noncoding RNAs. Annu Rev Biochem. 2018;87:323–50.

    Article  CAS  PubMed  Google Scholar 

  118. Sangrithi MN, Turner JMA. Mammalian X chromosome dosage compensation: perspectives from the germ line. BioEssays. 2018;40:e1800024.

    Article  PubMed  Google Scholar 

  119. Sawyer IA, Bartek J, Dundr M. Phase separated microenvironments inside the cell nucleus are linked to disease and regulate epigenetic state, transcription and RNA processing. Semin Cell Dev Biol. 2019;90:94–103.

    Article  CAS  PubMed  Google Scholar 

  120. Shevtsov SP, Dundr M. Nucleation of nuclear bodies by RNA. Nat Cell Biol. 2011;13:167–73.

    Article  CAS  PubMed  Google Scholar 

  121. Shimada Y, Mohn F, Bühler M. The RNA-induced transcriptional silencing complex targets chromatin exclusively via interacting with nascent transcripts. Genes Dev. 2016;30:2571–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Splinter E, de Wit E, Nora EP, Klous P, van de Werken HJ, Zhu Y, et al. The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes Dev. 2011;25:1371–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Spracklin G, Fields B, Wan G, Becker D, Wallig A, Shukla A, et al. The RNAi Inheritance Machinery of Caenorhabditis elegans. Genetics. 2017;206:1403–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22:96–118.

    Article  CAS  PubMed  Google Scholar 

  125. Stuwe E, Tóth KF, Aravin AA. Small but sturdy: small RNAs in cellular memory and epigenetics. Genes Dev. 2014;28:423–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sugiyama T, Cam HP, Sugiyama R, Noma K, Zofall M, Kobayashi R, et al. SHREC, an effector complex for heterochromatic transcriptional silencing. Cell. 2007;128:491–504.

    Article  CAS  PubMed  Google Scholar 

  127. Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT. Jpx RNA activates Xist by evicting CTCF. Cell. 2013;153:1537–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Sun Z, Bernstein E. Histone variant macroH2A: from chromatin deposition to molecular function. Essays Biochem. 2019;63:59–74.

    Article  CAS  PubMed  Google Scholar 

  129. Tan FL, Yin JQ. RNAi, a new therapeutic strategy against viral infection. Cell Res. 2004;14:460–6.

    Article  CAS  PubMed  Google Scholar 

  130. Tanasijevic B, Rasmussen TP. X chromosome inactivation and differentiation occur readily in ES cells doubly-deficient for macroH2A1 and macroH2A2. PLoS ONE. 2011;6:e21512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Thakur J, Fang H, Llagas T, Disteche CM, Henikoff S. Architectural RNA is required for heterochromatin organization. bioRxiv 2019.

  132. Thakur J, Henikoff S. Architectural RNA in chromatin organization. Biochem Soc Trans. 2020;48:1967–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Thakur J, Packiaraj J, Henikoff S. Sequence, chromatin and evolution of satellite DNA. IJMS. 2021;22:4309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Tian D, Sun S, Lee JT. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell. 2010;143:390–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Topp CN, Zhong CX, Dawe RK. Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci USA. 2004;101:15986–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329:689–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Turner BM, Birley AJ, Lavender J. Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell. 1992;69:375–84.

    Article  CAS  PubMed  Google Scholar 

  138. Valgardsdottir R, Chiodi I, Giordano M, Cobianchi F, Riva S, Biamonti G. Structural and functional characterization of noncoding repetitive RNAs transcribed in stressed human cells. Mol Biol Cell. 2005;16:2597–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Valgardsdottir R, Chiodi I, Giordano M, Rossi A, Bazzini S, Ghigna C, et al. Transcription of satellite III non-coding RNAs is a general stress response in human cells. Nucleic Acids Res. 2008;36:423–34.

    Article  CAS  PubMed  Google Scholar 

  140. van den Berg IM, Laven JS, Stevens M, Jonkers I, Galjaard RJ, Gribnau J, et al. X chromosome inactivation is initiated in human preimplantation embryos. Am J Hum Genet. 2009;84:771–9.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Vastenhouw NL, Brunschwig K, Okihara KL, Müller F, Tijsterman M, Plasterk RH. Gene expression: long-term gene silencing by RNAi. Nature. 2006;442:882.

    Article  CAS  PubMed  Google Scholar 

  142. Velazquez Camacho O, Galan C, Swist-Rosowska K, Ching R, Gamalinda M, Karabiber F, et al. Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation. Elife. 2017. https://doi.org/10.7554/eLife.25293.

  143. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science. 2004;303:672–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science. 2002;297:1833–7.

    Article  CAS  PubMed  Google Scholar 

  145. Wang J, Jia ST, Jia S. New insights into the regulation of heterochromatin. Trends Genet. 2016;32:284–94.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Wang Y, Zhang W, Jin Y, Johansen J, Johansen KM. The JIL-1 tandem kinase mediates histone H3 phosphorylation and is required for maintenance of chromatin structure in Drosophila. Cell. 2001;105:433–43.

    Article  CAS  PubMed  Google Scholar 

  147. Watts BR, Wittmann S, Wery M, Gautier C, Kus K, Birot A, et al. Histone deacetylation promotes transcriptional silencing at facultative heterochromatin. Nucleic Acids Res. 2018;46:5426–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Weber SC, Brangwynne CP. Getting RNA and protein in phase. Cell. 2012;149:1188–91.

    Article  CAS  PubMed  Google Scholar 

  149. Wei X, Eickbush DG, Speece I, Larracuente AM. Heterochromatin-dependent transcription of satellite DNAs in the. Elife. 2021. https://doi.org/10.7554/eLife.62375.

  150. Wong AK, Rattner JB. Sequence organization and cytological localization of the minor satellite of mouse. Nucleic Acids Res. 1988;16:11645–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Wong LH, Brettingham-Moore KH, Chan L, Quach JM, Anderson MA, Northrop EL, et al. Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res. 2007;17:1146–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Wutz A. Noncoding roX RNA remodeling triggers fly dosage compensation complex assembly. Mol Cell. 2013;51:131–2.

    Article  CAS  PubMed  Google Scholar 

  153. Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet. 2002;30:167–74.

    Article  CAS  PubMed  Google Scholar 

  154. Xu N, Donohoe ME, Silva SS, Lee JT. Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein. Nat Genet. 2007;39:1390–6.

    Article  CAS  PubMed  Google Scholar 

  155. Xu N, Tsai CL, Lee JT. Transient homologous chromosome pairing marks the onset of X inactivation. Science. 2006;311:1149–52.

    Article  CAS  PubMed  Google Scholar 

  156. Yu R, Wang X, Moazed D. Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation. Nature. 2018;558:615–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Zhang R, Erler J, Langowski J. Histone acetylation regulates chromatin accessibility: role of H4K16 in inter-nucleosome interaction. Biophys J. 2017;112:450–9.

    Article  CAS  PubMed  Google Scholar 

  158. Zhang Z, Wang J, Schultz N, Zhang F, Parhad SS, Tu S, et al. The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell. 2014;157:1353–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322:750–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Zheng H, Xie W. The role of 3D genome organization in development and cell differentiation. Nat Rev Mol Cell Biol. 2019;20:535–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

JT is supported by the Department of Biology, Emory University start-up funds.

Author information

Authors and Affiliations

  1. Department of Biology, Emory University, 1510 Clifton Rd #2006, Atlanta, GA, 30322, USA

    Kaitlyn Morgan Heyt & Jitendra Thakur

Authors
  1. Kaitlyn Morgan Heyt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jitendra Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KMH wrote the manuscript, KMH and JT conceptualized and edited the manuscript.

Corresponding author

Correspondence to Jitendra Thakur.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Images

Images are generated using BioRender.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding Editor: Somnath Paul; Reviewers: Subhash C Lakhotia, Sharad Awasthi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heyt, K.M., Thakur, J. Regulation of epigenetic processes by non-coding RNAs. Nucleus 64, 285–301 (2021). https://doi.org/10.1007/s13237-021-00372-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13237-021-00372-1

Keywords

Search

Navigation