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Cell Rep. 2014 Nov 6;9(3):1163-70. doi: 10.1016/j.celrep.2014.10.018. Epub 2014 Oct 30.

Quantitative ChIP-Seq normalization reveals global modulation of the epigenome.

Author information

1
Syros Pharmaceuticals, 480 Arsenal Street, Watertown, MA 02472, USA. Electronic address: dorlando@syros.com.
2
Syros Pharmaceuticals, 480 Arsenal Street, Watertown, MA 02472, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
4
Syros Pharmaceuticals, 480 Arsenal Street, Watertown, MA 02472, USA. Electronic address: mguenther@syros.com.

Abstract

Epigenomic profiling by chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) is a prevailing methodology used to investigate chromatin-based regulation in biological systems such as human disease, but the lack of an empirical methodology to enable normalization among experiments has limited the precision and usefulness of this technique. Here, we describe a method called ChIP with reference exogenous genome (ChIP-Rx) that allows one to perform genome-wide quantitative comparisons of histone modification status across cell populations using defined quantities of a reference epigenome. ChIP-Rx enables the discovery and quantification of dynamic epigenomic profiles across mammalian cells that would otherwise remain hidden using traditional normalization methods. We demonstrate the utility of this method for measuring epigenomic changes following chemical perturbations and show how reference normalization of ChIP-seq experiments enables the discovery of disease-relevant changes in histone modification occupancy.

PMID:
25437568
DOI:
10.1016/j.celrep.2014.10.018
[Indexed for MEDLINE]
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