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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.

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Change history

  • 23 March 2011

    Author initials were corrected for T.K.C.


Primary accessions

Gene Expression Omnibus


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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

Author notes

    • Yuri B. Schwartz
    • , Daniela Linder-Basso
    •  & Gregory Shanower

    Present addresses: Department of Molecular Biology, Umea University, 901 87 Umea, Sweden. (Y.B.S.); Department of Plant Biology and Pathology, SEBS, Rutgers University, New Brunswick, New Jersey 08901, USA (D.L.-B.); Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania 18510, USA (G.S.).

    • Gary H. Karpen
    •  & Peter J. Park

    These authors contributed equally to this work.


  1. Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Peter V. Kharchenko
    • , Michael Y. Tolstorukov
    • , Lovelace J. Luquette
    • , Ruibin Xi
    • , Youngsook L. Jung
    • , Richard W. Park
    • , Eric P. Bishop
    •  & Peter J. Park
  2. Children’s Hospital Informatics Program, Boston, Massachusetts 02115, USA

    • Peter V. Kharchenko
    • , Michael Y. Tolstorukov
    •  & Peter J. Park
  3. Division of Genetics, Department of Medicine, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA

    • Artyom A. Alekseyenko
    • , Erica Larschan
    • , Andrey A. Gorchakov
    • , Annette Plachetka
    • , Youngsook L. Jung
    • , Mitzi I. Kuroda
    •  & Peter J. Park
  4. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Artyom A. Alekseyenko
    • , Erica Larschan
    • , Andrey A. Gorchakov
    • , Annette Plachetka
    •  & Mitzi I. Kuroda
  5. Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA

    • Yuri B. Schwartz
    • , Daniela Linder-Basso
    • , Gregory Shanower
    •  & Vincenzo Pirrotta
  6. Department of Molecular and Cell Biology, University of California at Berkeley, and Department of Genome Dynamics, Lawrence Berkeley National Lab, Berkeley, California 94720, USA

    • Aki Minoda
    •  & Gary H. Karpen
  7. Department of Biology, Washington University in St Louis, St Louis, Missouri 63130, USA

    • Nicole C. Riddle
    • , Tingting Gu
    •  & Sarah C. R. Elgin
  8. MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA

    • Jason Ernst
    •  & Manolis Kellis
  9. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA

    • Jason Ernst
    •  & Manolis Kellis
  10. Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

    • Peter J. Sabo
    • , Theresa K. Canfield
    • , Richard Sandstrom
    • , Robert E. Thurman
    •  & John A. Stamatoyannopoulos
  11. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02906, USA

    • Erica Larschan
  12. Graduate Program in Bioinformatics, Boston University, Boston, Massachusetts 02115, USA

    • Richard W. Park
    •  & Eric P. Bishop
  13. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA

    • David M. MacAlpine
  14. Department of Medicine, University of Washington, Seattle, Washington 98195, USA

    • John A. Stamatoyannopoulos


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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

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

The data are available from the modENCODE site ( GRO-Seq data are available from Gene Expression Omnibus (GEO, GSE25321).

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    Supplementary Figures

    This file contains Supplementary Figures 1-35 with legends.

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    Supplementary Information

    This file contains Supplementary Tables 1-6 and Supplementary Sections 1-2.

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