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Mol Cell DOI:10.1016/j.molcel.2015.11.003

A Multiplexed System for Quantitative Comparisons of Chromatin Landscapes.

Publication TypeJournal Article
Year of Publication2016
Authorsvan Galen, P, Viny, AD, Ram, O, Ryan, RJH, Cotton, MJ, Donohue, L, Sievers, C, Drier, Y, Liau, BB, Gillespie, SM, Carroll, KM, Cross, MB, Levine, RL, Bernstein, BE
JournalMol Cell
Date Published2016 Jan 07
KeywordsChromatin, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, DNA Barcoding, Taxonomic, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cells, High-Throughput Nucleotide Sequencing, Histones, Humans, K562 Cells, Leukemia, Multiplex Polymerase Chain Reaction, Mutation

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.


Alternate JournalMol. Cell
PubMed ID26687680
PubMed Central IDPMC4707994
Grant ListU54 HG006991 / HG / NHGRI NIH HHS / United States
U01 HL100395 / HL / NHLBI NIH HHS / United States
HG006991 / HG / NHGRI NIH HHS / United States
U54 HG004570 / HG / NHGRI NIH HHS / United States
HG006193 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U01HL100395 / HL / NHLBI NIH HHS / United States