Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Resource
  • Published:

Pol II and its associated epigenetic marks are present at Pol III–transcribed noncoding RNA genes

Nature Structural & Molecular Biology volume 17, pages 629–634 (2010)Cite this article

Subjects

Abstract

Epigenetic control is an important aspect of gene regulation. Despite detailed understanding of protein-coding gene expression, the transcription of noncoding RNA genes by RNA polymerase III (Pol III) is less well characterized. Here we profile the epigenetic features of Pol III target genes throughout the human genome. This reveals that the chromatin landscape of Pol III–transcribed genes resembles that of Pol II templates in many ways, although there are also clear differences. Our analysis also uncovered an entirely unexpected phenomenon: namely, that Pol II is present at the majority of genomic loci that are bound by Pol III.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chromatin environment of Pol III genes.
Figure 2: Pol III target genes are associated with both similar and distinct chromatin features to Pol II target genes.
Figure 3: Tissue-specific expression of tRNA genes.
Figure 4: Novel Pol III binding sites.
Figure 5: Pol II is present at Pol III–transcribed genes.
Figure 6: Levels of 5S rRNA and pre-tRNAs are decreased by 4-h treatment with α-amanitin oleate.

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Dieci, G. et al. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614–622 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Maida, Y. et al. An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 461, 230–235 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yang, Z. et al. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414, 317–322 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Nguyen, V.T. et al. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414, 322–325 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Mossink, M.H., van Zon, A., Scheper, R.J., Sonneveld, P. & Wiemer, E.A.C. Vaults: a ribonucleoprotein particle involved in drug resistance? Oncogene 22, 7458–7467 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Borchert, G.M., Lanier, W. & Davidson, B.L. RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol. Biol. 13, 1097–1101 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Ozsolak, F. et al. Chromatin structure analyses identify miRNA promoters. Genes Dev. 22, 3172–3183 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li, B., Carey, M. & Workman, J.L. The role of chromatin during transcription. Cell 128, 707–719 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. McStay, B. & Grummt, I. The epigenetics of rRNA genes: from molecular to chromosome biology. Annu. Rev. Cell Dev. Biol. 24, 131–157 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Mikkelsen, T.S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, Z. et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40, 897–903 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Muse, G.W. et al. RNA polymerase is poised for activation across the genome. Nat. Genet. 39, 1507–1511 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zeitlinger, J. et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat. Genet. 39, 1512–1516 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bernstein, B.E., Meissner, A. & Lander, E.S. The mammalian epigenome. Cell 128, 669–681 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Li, J., Moazed, D. & Gygi, S.P. Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation. J. Biol. Chem. 277, 49383–49388 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Roberts, D.N. & Stewart, A.J. Huff, J. T. & Cairns, B. R. The RNA polymerase III transcriptome revealed by genome-wide localization and activity-occupancy relationships. Proc. Natl. Acad. Sci. USA 100, 14695–14700 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kenneth, N.S. et al. TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription. Proc. Natl. Acad. Sci. USA 104, 14917–14922 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dittmar, K.A., Goodenbour, J.M. & Pan, T. Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2, e221 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bortolin-Cavaille, M.L., Dance, M., Weber, M. & Cavaille, J. C19MC microRNAs are processed from introns of large pol-II, non-protein-coding transcripts. Nucleic Acids Res. 37, 3464–3473 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Barski, A. et al. Chromatin poises miRNA- and protein-coding genes for expression. Genome Res. 19, 1742–1751 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Berezikov, E., Cuppen, E. & Plasterk, R.H. Approaches to microRNA discovery. Nat. Genet. 38 (Suppl), S2–S7 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Jothi, R., Cuddapah, S., Barski, A., Cui, K. & Zhao, K. Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data. Nucleic Acids Res. 36, 5221–5231 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Listerman, I., Bledau, A.S., Grishina, I. & Neugebauer, K.M. Extragenic accumulation of RNA polymerase II enhances transcription by RNA polymerase III. PLoS Genet. 3, e212 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mertens, C. & Roeder, R.G. Different functional modes of p300 in activation of RNA polymerase III transcription from chromatin templates. Mol. Cell. Biol. 28, 5764–5776 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee, D.Y., Hayes, J.J., Pruss, D. & Wolffe, A.P. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72, 73–84 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Ura, K., Kurumizaka, H., Dimitrov, S., Almouzni, G. & Wolffe, A.P. Histone acetylation: influence on transcription, nucleosome mobility and positioning, and linker histone-dependent transcriptional repression. EMBO J. 16, 2096–2107 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Howe, L., Ranalli, T.A., Allis, C.D. & Ausio, J. Transcriptionally active Xenopus laevis somatic 5 S ribosomal RNA genes are packaged with hyperacetylated histone H4, whereas transcriptionally silent oocyte genes are not. J. Biol. Chem. 273, 20693–20696 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Tse, C., Sera, T., Wolffe, A.P. & Hansen, J.C. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Mol. Cell. Biol. 18, 4629–4638 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kundu, T.K., Wang, Z. & Roeder, R.G. Human TFIIIC relieves chromatin-mediated repression of RNA polymerase III transcription and contains an intrinsic histone acetyltransferase activity. Mol. Cell. Biol. 19, 1605–1615 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hernandez, N. TBP, a universal eukaryotic transcription factor? Genes Dev. 7, 1291–1308 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Gomez-Roman, N., Grandori, C., Eisenman, R.N. & White, R.J. Direct activation of RNA polymerase III transcription by c-Myc. Nature 421, 290–294 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Ghavi-Helm, Y. et al. Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription. Genes Dev. 22, 1934–1947 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lunyak, V.V. Boundaries. Boundaries...Boundaries??? Curr. Opin. Cell Biol. 20, 281–287 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Haldar, D. & Kamakaka, R.T. tRNA genes as chromatin barriers. Nat. Struct. Mol. Biol. 13, 192–193 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Donze, D. & Kamakaka, R.T. RNA polymerase III and RNA polymerase II promoter complexes are heterochromatin barriers in Saccharomyces cerevisiae. EMBO J. 20, 520–531 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Oki, M. & Kamakaka, R.T. Barrier function at HMR. Mol. Cell 19, 707–716 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Scott, K.C., Merrett, S.L. & Willard, H.F. A heterochromatin barrier partitions the fission yeast centromere into discrete chromatin domains. Curr. Biol. 16, 119–129 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Noma, K., Cam, H.P., Maraia, R.J. & Grewal, S.I.S. A role for TFIIIC transcription factor complex in genome organization. Cell 125, 859–872 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Daniels, G.R. & Deininger, P.L. Repeat sequence families derived from mammalian tRNA genes. Nature 317, 819–822 (1985).

    Article  CAS  PubMed  Google Scholar 

  42. Ferrigno, O. et al. Transposable B2 SINE elements can provide mobile RNA polymerase II promoters. Nat. Genet. 28, 77–81 (2001).

    CAS  PubMed  Google Scholar 

  43. West, A.G., Huang, S., Gaszner, M., Litt, M.D. & Felsenfeld, G. Recruitment of histone modifications by USF proteins at a vertebrate barrier element. Mol. Cell 16, 453–463 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Willoughby, D.A., Vilalta, A. & Oshima, R.G. An Alu element from the K18 gene confers position-independent expression in transgenic mice. J. Biol. Chem. 275, 759–768 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Geyer, P.K. The role of insulator elements in defining domains of gene expression. Curr. Opin. Genet. Dev. 7, 242–248 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Chepelev, I., Wei, G., Tang, Q. & Zhao, K. Detection of single nucleotide variations in expressed exons of the human genome using RNA-Seq. Nucleic Acids Res. 37, e106 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Daly, N.L. et al. Deregulation of RNA polymerase III transcription in cervical epithelium in response to high-risk human papillomavirus. Oncogene 24, 880–888 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Winter, A.G. et al. RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors. Proc. Natl. Acad. Sci. USA 97, 12619–12624 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank D.E. Schones for assistance with the Solexa Pipeline analysis and helpful discussions. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Heart, Lung, and Blood Institute (K.Z.) and Cancer Research UK (R.J.W.). A.B. was additionally supported by 1K22HL098691-01 Career Transition Award from the National Heart, Lung, and Blood Institute, US National Institutes of Health.

Author information

Author notes

  1. Artem Barski and Iouri Chepelev: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

    Artem Barski, Iouri Chepelev, Suresh Cuddapah, Kairong Cui & Keji Zhao

  2. Beatson Institute for Cancer Research, Glasgow, UK

    Dritan Liko, Alastair B Fleming, Joanna Birch & Robert J White

Authors
  1. Artem Barski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iouri Chepelev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dritan Liko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suresh Cuddapah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alastair B Fleming
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joanna Birch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kairong Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert J White
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keji Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.B., I.C., R.J.W. and K.Z. designed the study and wrote the paper; A.B., D.L., S.C., A.B.F., J.B. and K.C. performed the experiments; I.C. and A.B. analyzed the data.

Corresponding authors

Correspondence to Robert J White or Keji Zhao.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1 and 2, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 1099 kb)

Supplementary Table 3

Novel pol III, TFIIIB and TFIIIC binding sites in HeLa cells (XLS 66 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barski, A., Chepelev, I., Liko, D. et al. Pol II and its associated epigenetic marks are present at Pol III–transcribed noncoding RNA genes. Nat Struct Mol Biol 17, 629–634 (2010). https://doi.org/10.1038/nsmb.1806

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.1806

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing