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Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors

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Abstract

Current methods for whole-genome mapping of protein-DNA interactions, performed by coupling chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), require large amounts of starting materials, which precludes their application to rare cell types. Here we combine a high-sensitivity ChIP assay with a new library preparation procedure to map histone modifications in as few as 10,000 cells. We used the technique to characterize mouse hematopoietic progenitors and thereby gain insight into their developmental program.

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Figure 1: Preparation of sequencing library from small amounts of immunoprecipitated DNA.
Figure 2: Validation of small-cell-number ChIP-seq maps.
Figure 3: Chromatin domains at developmental regulators in hematopoietic progenitors.

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Acknowledgements

We thank D. Flowers and I. Bernstein for expertise, reagents and assistance in isolation of hematopoietic cells, N. Shoresh and T. Mikkelsen for computational assistance and B. Knoechel, E. Mendenhall, A. Goren and A. Chi for constructive discussions and critical reading of the manuscript. This research was supported by funds from the Starr Cancer Consortium, a Charles E. Culpeper Scholarship, the US National Human Genome Research Institute, the National Institutes of Health Roadmap for Epigenomics and the National Heart, Lung, and Blood Institute.

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Authors and Affiliations

  1. Department of Pathology, Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Mazhar Adli, Jiang Zhu & Bradley E Bernstein

  2. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Mazhar Adli, Jiang Zhu & Bradley E Bernstein

  3. Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts, USA

    Mazhar Adli, Jiang Zhu & Bradley E Bernstein

Authors
  1. Mazhar Adli
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  2. Jiang Zhu
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  3. Bradley E Bernstein
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Contributions

M.A. and B.E.B. designed the method. M.A. performed the experiments. M.A., J.Z. and B.E.B. analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Bradley E Bernstein.

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Competing interests

M.A. and B.E.B. have filed a patent application describing the methods presented here (US 12/699,508).

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Supplementary Figures 1–7 and Supplementary Tables 1–3 (PDF 4521 kb)

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Adli, M., Zhu, J. & Bernstein, B. Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors. Nat Methods 7, 615–618 (2010). https://doi.org/10.1038/nmeth.1478

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  • DOI: https://doi.org/10.1038/nmeth.1478

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