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

Julie Brind’Amour, Sheng Liu, Matthew Hudson, Carol Chen, Mohammad M. Karimi and Matthew C. Lorincz ()
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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
Matthew C. Lorincz: Life Sciences Institute, The University of British Columbia

Nature Communications, 2015, vol. 6, issue 1, 1-8

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7033

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