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.

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

This article has been updated

Abstract

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Chromatin annotation of the Drosophila melanogaster genome.
Figure 2: Visualization of spatial scales and organization using compact folding.
Figure 3: Chromatin patterns associated with transcriptionally active genes.
Figure 4: Signatures of TSSs within domains of Polycomb-mediated repression.
Figure 5: Chromatin signatures of regulatory elements identified by DNase I hypersensitivity.
Figure 6: Spatial arrangements of chromatin states associated with active transcription.

Accession codes

Primary accessions

Gene Expression Omnibus

Change history

  • 23 March 2011

    Author initials were corrected for T.K.C.

References

  1. modENCODE Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 10.1126/science.1198374. (in the press)

  2. Gerstein, M. B. et al. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 10.1126/science.1196914. (in the press)

  3. Adams, M. D. et al. The genome sequence of Drosophila melanogaster . Science 287, 2185–2195 (2000)

    Article  PubMed  Google Scholar 

  4. Clark, A. G. et al. Evolution of genes and genomes on the Drosophila phylogeny. Nature 450, 203–218 (2007)

    ADS  Article  PubMed  Google Scholar 

  5. Hoskins, R. A. et al. Sequence finishing and mapping of Drosophila melanogaster heterochromatin. Science 316, 1625–1628 (2007)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Tweedie, S. et al. FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res. 37, D555–D559 (2009)

    CAS  Article  PubMed  Google Scholar 

  7. Felsenfeld, G. & Groudine, M. Controlling the double helix. Nature 421, 448–453 (2003)

    ADS  Article  PubMed  Google Scholar 

  8. Mendenhall, E. M. & Bernstein, B. E. Chromatin state maps: new technologies, new insights. Curr. Opin. Genet. Dev. 18, 109–115 (2008)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Egelhofer, T. A. et al. An assessment of histone-modification antibody quality. Nature Struct. Mol. Biol. 10.1038/nsmb.1972 (5 December 2010)

  10. Eissenberg, J. C. & Reuter, G. Cellular mechanism for targeting heterochromatin formation in Drosophila . Int. Rev. Cell Mol. Biol. 273, 1–47 (2009)

    CAS  Article  PubMed  Google Scholar 

  11. Schwartz, Y. B. & Pirrotta, V. Polycomb complexes and epigenetic states. Curr. Opin. Cell Biol. 20, 266–273 (2008)

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  13. Liu, C. L. et al. Single-nucleosome mapping of histone modifications in S. cerevisiae . PLoS Biol. 3, e328 (2005)

    Article  PubMed  PubMed Central  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  15. Larschan, E. et al. MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism. Mol. Cell 28, 121–133 (2007)

    CAS  Article  PubMed  Google Scholar 

  16. Riddle, N. C. et al. Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. 10.1101/gr.110098.110. (in the press)

  17. Anders, S. Visualization of genomic data with the Hilbert curve. Bioinformatics 25, 1231–1235 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. MacAlpine, D. M., Rodriguez, H. K. & Bell, S. P. Coordination of replication and transcription along a Drosophila chromosome. Genes Dev. 18, 3094–3105 (2004)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Blumenthal, A. B., Kriegstein, H. J. & Hogness, D. S. The units of DNA replication in Drosophila melanogaster chromosomes. Cold Spring Harb. Symp. Quant. Biol. 38, 205–223 (1974)

    CAS  Article  PubMed  Google Scholar 

  20. Ernst, J. & Kellis, M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nature Biotechnol. 28, 817–825 (2010)

    CAS  Article  Google Scholar 

  21. Misulovin, Z. et al. Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome. Chromosoma 117, 89–102 (2008)

    CAS  Article  PubMed  Google Scholar 

  22. Kagey, M. H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430–435 (2010)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Deal, R. B., Henikoff, J. G. & Henikoff, S. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science 328, 1161–1164 (2010)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Henikoff, S., Henikoff, J. G., Sakai, A., Loeb, G. B. & Ahmad, K. Genome-wide profiling of salt fractions maps physical properties of chromatin. Genome Res. 19, 460–469 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. MacAlpine, H. K., Gordan, R., Powell, S. K., Hartemink, A. J. & MacAlpine, D. M. Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading. Genome Res. 20, 201–211 (2010)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Visel, A. et al. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457, 854–858 (2009)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Zinzen, R. P., Girardot, C., Gagneur, J., Braun, M. & Furlong, E. E. Combinatorial binding predicts spatio-temporal cis-regulatory activity. Nature 462, 65–70 (2009)

    ADS  CAS  Article  PubMed  Google Scholar 

  28. Schwartz, Y. B. et al. Genome-wide analysis of Polycomb targets in Drosophila melanogaster . Nature Genet. 38, 700–705 (2006)

    CAS  Article  PubMed  Google Scholar 

  29. Schwartz, Y. B. et al. Alternative epigenetic chromatin states of Polycomb target genes. PLoS Genet. 6, e1000805 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nechaev, S. et al. Global analysis of short RNAs reveals widespread promoter-proximal stalling and arrest of Pol II in Drosophila . Science 327, 335–338 (2010)

    ADS  CAS  Article  PubMed  Google Scholar 

  31. Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322, 1845–1848 (2008)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Wu, C. The 5′ ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286, 854–860 (1980)

    ADS  CAS  Article  PubMed  Google Scholar 

  33. Wu, C., Bingham, P. M., Livak, K. J., Holmgren, R. & Elgin, S. C. The chromatin structure of specific genes: I. Evidence for higher order domains of defined DNA sequence. Cell 16, 797–806 (1979)

    CAS  Article  PubMed  Google Scholar 

  34. Elgin, S. C. The formation and function of DNase I hypersensitive sites in the process of gene activation. J. Biol. Chem. 263, 19259–19262 (1988)

    CAS  PubMed  Google Scholar 

  35. Jin, C. et al. H3.3/H2A.Z double variant-containing nucleosomes mark ‘nucleosome-free regions’ of active promoters and other regulatory regions. Nature Genet. 41, 941–945 (2009)

    CAS  Article  PubMed  Google Scholar 

  36. Hesselberth, J. R. et al. Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nature Methods 6, 283–289 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Heintzman, N. D. et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108–112 (2009)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. MacArthur, S. et al. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol. 10, R80 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kim, T. K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182–187 (2010)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Filion, G. J. et al. Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143, 212–224 (2010)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006)

    CAS  Article  PubMed  Google Scholar 

  42. Kanhere, A. et al. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell 38, 675–688 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Schuettengruber, B. et al. Functional anatomy of polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol. 7, e13 (2009)

    Article  PubMed  Google Scholar 

  44. Sekimata, M. et al. CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-γ locus. Immunity 31, 551–564 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Cherbas, L. et al. The transcriptional diversity of 25 Drosophila cell lines. Genome Res. 21 10.1101/gr.112961.110 (in the press)

  46. Gravely, B. R. et al. The developmental transcriptome of Drosophila melanogaster . Nature 10.1038/nature09715 (this issue).

  47. Clemens, J. C. et al. Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. Proc. Natl Acad. Sci. USA 97, 6499–6503 (2000)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank our technicians D. Acevedo, S. Gadel, C. Kennedy, O.-K. Lee, S. Marchetti, S. Vong and M. Weaver, and Rutgers BRTC. We also thank our colleagues who donated antibodies: J. Kadonaga (H1), A. L. Greenleaf (RNA pol II), G. Reuter (SU(VAR)3-9), G. Cavalli (GAF) and I. F. Zhimulev/H. Saumweber (Chromator). The major support for this work came from the modENCODE grant U01HG004258 to G.H.K. (Principal Investigator) and S.C.R.E., M.I.K., P.J.P. and V.P. (co-Principal Investigators), administered under Department of Energy contract no. DE-AC02-05CH11231. Additional funding came from RC2 HG005639, U01 HG004279, R01 GM082798, R37 GM45744, RC1 HG005334, R01 GM071923, U54 HG004592 and NSF 0905968.

Author information

Authors and Affiliations

Authors

Contributions

P.V.K. performed most bioinformatic analysis. A.A.A., Y.B.S., A.M., N.C.R., E.L., A.A.G., T.G., D.L.-B., A.P. and G.S. generated data, directed by S.C.R.E., M.I.K., V.P. and G.H.K. The 30-state analysis was performed by J.E. and M.K., whereas M.Y.T., L.J.L., R.X., Y.L.J., R.W.P. and E.P.B. performed additional bioinformatic analysis. P.J.S., T.K.C., R.S., R.E.T. and J.A.S. generated and processed DHS data. D.M.M. helped with replication analysis. P.J.P. supervised all analysis. G.H.K. coordinated the entire project. P.V.K., G.H.K. and P.J.P. wrote the manuscript, with contributions from S.C.R.E., M.I.K., V.P., Y.B.S, N.C.R, A.A.A. and A.M.

Corresponding authors

Correspondence to Gary H. Karpen or Peter J. Park.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

The data are available from the modENCODE site (http://www.modencode.org). GRO-Seq data are available from Gene Expression Omnibus (GEO, GSE25321).

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-35 with legends. (PDF 27107 kb)

Supplementary Information

This file contains Supplementary Tables 1-6 and Supplementary Sections 1-2. (PDF 18112 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kharchenko, P., Alekseyenko, A., Schwartz, Y. et al. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471, 480–485 (2011). https://doi.org/10.1038/nature09725

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature09725

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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