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Updated: Dec 25, 2025

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin
10:05

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin

Published on: January 20, 2016

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Loci specific epigenetic drug sensitivity

Thanutra Zhang1, Anna Pilko1,2, Roy Wollman1,2

  • 1Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA.

Nucleic Acids Research
|April 5, 2020
PubMed

Insights

New platform reveals locus-specific drug sensitivities for epigenetic modulators (epi-drugs). This advances understanding of how epi-drugs affect gene expression, paving the way for targeted therapies.

Area of Science:

  • Epigenetics and Genomics
  • Chemical Biology
  • Drug Discovery

Background:

  • Therapeutic targeting of epigenetic modulators (epi-drugs) presents a novel treatment strategy for various diseases.
  • The precise mechanisms underlying cellular changes induced by epi-drugs remain unclear, particularly the extent of global versus locus-specific effects.

Purpose of the Study:

  • To develop a platform for systematically investigating epi-drug sensitivity at numerous genomic locations.
  • To differentiate between cell-wide and disease-related locus-specific effects of epi-drugs.

Main Methods:

  • Combined DNA barcoding, unique split-pool encoding, and single-cell expression measurements.
  • Integrated internal controls to isolate locus-specific effects from global drug consequences.
  • Leveraged ENCODE data on chromatin modification.

Main Results:

  • Discovered widespread locus-specific sensitivities to three distinct epi-drugs targeting histone deacetylase, DNA methylation, and bromodomain proteins.
  • Identified specific chromatin environment features susceptible to epi-drug action.
  • Demonstrated the platform's capability to simultaneously assess hundreds of genomic locations.

Conclusions:

  • Locus-specific drug sensitivities are prevalent and predictable based on chromatin features.
  • This platform enables precise measurement of epi-drug effects, crucial for developing targeted therapies.
  • Findings support the advancement of personalized medicine through tailored epigenetic drug treatments.

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