A multiplexed system for quantitative comparisons of chromatin landscapes Journal Article

Authors: van Galen, P.; Viny, A. D.; Ram, O.; Ryan, R. J. H.; Cotton, M. J.; Donohue, L.; Sievers, C.; Drier, Y.; Liau, B. B.; Gillespie, S. M.; Carroll, K. M.; Cross, M. B.; Levine, R. L.; Bernstein, B. E.
Article Title: A multiplexed system for quantitative comparisons of chromatin landscapes
Abstract: Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large amounts of starting material, and involves tedious processing of each individual sample. Here, we address these limitations with a technology that leverages DNA barcoding to profile chromatin quantitatively and in multiplexed format. We concurrently map relative levels of multiple histone modifications across multiple samples, each comprising as few as a thousand cells. We demonstrate the technology by monitoring dynamic changes following inhibition of p300, EZH2, or KDM5, by linking altered epigenetic landscapes to chromatin regulator mutations, and by mapping active and repressive marks in purified human hematopoietic stem cells. Hence, this technology enables quantitative studies of chromatin state dynamics across rare cell types, genotypes, environmental conditions, and drug treatments. van Galen et al. introduce an approach for multiplexed ChIP-seq on small cell numbers. The approach allows quantitative comparisons of global and locus-specific histone modification levels. The technology is demonstrated by mapping hematopoietic stem cell chromatin landscapes and quantifying changes in leukemia cells treated with epigenetic inhibitors. © 2016 Elsevier Inc.
Journal Title: Molecular Cell
Volume: 61
Issue: 1
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2016-01-07
Start Page: 170
End Page: 180
Language: English
DOI: 10.1016/j.molcel.2015.11.003
PROVIDER: scopus
PMCID: PMC4707994
PUBMED: 26687680
Notes: Article -- Export Date: 3 February 2016 -- Source: Scopus
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MSK Authors
  1. Ross Levine
    490 Levine
  2. Aaron David Viny
    23 Viny