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, Matthew C. Lorincz

Research output: Contribution to journalArticle

94 Citations (Scopus)

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 x 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.

Original languageEnglish
Article number6033
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 21 Jan 2015
Externally publishedYes

Fingerprint

nuclease
Micrococcal Nuclease
chromatin
sequencing
genome
Chromatin Immunoprecipitation
Histone Code
Chromatin
Genes
Cells
Genome
Histones
Population
stem cells
embryos
Embryonic Stem Cells
profiles
cells
cultured cells
Epigenomics

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations. / Brind'Amour, Julie; Liu, Sheng; Hudson, Matthew; Chen, Carol; Karimi, Mohammad M.; Lorincz, Matthew C.

In: Nature Communications, Vol. 6, 6033, 21.01.2015.

Research output: Contribution to journalArticle

Brind'Amour, Julie ; Liu, Sheng ; Hudson, Matthew ; Chen, Carol ; Karimi, Mohammad M. ; Lorincz, Matthew C. / An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations. In: Nature Communications. 2015 ; Vol. 6.
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