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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells

Author

Listed:
  • Tarjei S. Mikkelsen

    (Broad Institute of Harvard and MIT,
    MIT, and)

  • Manching Ku

    (Broad Institute of Harvard and MIT,
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • David B. Jaffe

    (Broad Institute of Harvard and MIT,)

  • Biju Issac

    (Broad Institute of Harvard and MIT,
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • Erez Lieberman

    (Broad Institute of Harvard and MIT,
    MIT, and)

  • Georgia Giannoukos

    (Broad Institute of Harvard and MIT,)

  • Pablo Alvarez

    (Broad Institute of Harvard and MIT,)

  • William Brockman

    (Broad Institute of Harvard and MIT,)

  • Tae-Kyung Kim

    (Children’s Hospital, and)

  • Richard P. Koche

    (Broad Institute of Harvard and MIT,
    MIT, and
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • William Lee

    (Broad Institute of Harvard and MIT,)

  • Eric Mendenhall

    (Broad Institute of Harvard and MIT,
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • Aisling O’Donovan

    (Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • Aviva Presser

    (Broad Institute of Harvard and MIT,)

  • Carsten Russ

    (Broad Institute of Harvard and MIT,)

  • Xiaohui Xie

    (Broad Institute of Harvard and MIT,)

  • Alexander Meissner

    (Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA)

  • Marius Wernig

    (Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA)

  • Rudolf Jaenisch

    (Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA)

  • Chad Nusbaum

    (Broad Institute of Harvard and MIT,)

  • Eric S. Lander

    (Broad Institute of Harvard and MIT,
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA)

  • Bradley E. Bernstein

    (Broad Institute of Harvard and MIT,
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Harvard Medical School, Boston, Massachusetts 02115, USA)

Abstract

We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.

Suggested Citation

  • Tarjei S. Mikkelsen & Manching Ku & David B. Jaffe & Biju Issac & Erez Lieberman & Georgia Giannoukos & Pablo Alvarez & William Brockman & Tae-Kyung Kim & Richard P. Koche & William Lee & Eric Mendenh, 2007. "Genome-wide maps of chromatin state in pluripotent and lineage-committed cells," Nature, Nature, vol. 448(7153), pages 553-560, August.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7153:d:10.1038_nature06008
    DOI: 10.1038/nature06008
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    6. Federica Baccini & Monica Bianchini & Filippo Geraci, 2022. "Graph-Based Integration of Histone Modification Profiles," Mathematics, MDPI, vol. 10(11), pages 1-15, May.
    7. Chet H. Loh & Siebe Genesen & Matteo Perino & Magnus R. Bark & Gert Jan C. Veenstra, 2021. "Loss of PRC2 subunits primes lineage choice during exit of pluripotency," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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    10. Linghua Zhou & Yong Shen & Libo Jiang & Danni Yin & Jingxin Guo & Hui Zheng & Hao Sun & Rongling Wu & Yunqian Guo, 2015. "Systems Mapping for Hematopoietic Progenitor Cell Heterogeneity," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-18, May.
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