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An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations

Author

Listed:
  • Julie Brind’Amour

    (Life Sciences Institute, The University of British Columbia)

  • Sheng Liu

    (Life Sciences Institute, The University of British Columbia)

  • Matthew Hudson

    (Life Sciences Institute, The University of British Columbia)

  • Carol Chen

    (Life Sciences Institute, The University of British Columbia)

  • Mohammad M. Karimi

    (Life Sciences Institute, The University of British Columbia
    Biomedical Research Centre, The University of British Columbia)

  • Matthew C. Lorincz

    (Life Sciences Institute, The University of British Columbia)

Abstract

Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required to generate high-quality data sets, precluding the study of rare cell populations. Here, we present an ultra-low-input micrococcal nuclease-based native ChIP (ULI-NChIP) and sequencing method to generate genome-wide histone mark profiles with high resolution from as few as 103 cells. We demonstrate that ULI-NChIP-seq generates high-quality maps of covalent histone marks from 103 to 106 embryonic stem cells. Subsequently, we show that ULI-NChIP-seq H3K27me3 profiles generated from E13.5 primordial germ cells isolated from single male and female embryos show high similarity to recent data sets generated using 50–180 × more material. Finally, we identify sexually dimorphic H3K27me3 enrichment at specific genic promoters, thereby illustrating the utility of this method for generating high-quality and -complexity libraries from rare cell populations.

Suggested Citation

  • Julie Brind’Amour & Sheng Liu & Matthew Hudson & Carol Chen & Mohammad M. Karimi & Matthew C. Lorincz, 2015. "An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations," Nature Communications, Nature, vol. 6(1), pages 1-8, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7033
    DOI: 10.1038/ncomms7033
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