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Assays & screens

Coupled ligand affinity capture and massively parallel DNA sequencing (Chem-seq) for genome-wide mapping of interactions between small molecules and chromatin

Chem-seq can help map interactions between small molecules and their protein targets in chromatin of cells. In Chem-seq, cells are first treated with an affinity capture-capable analog of a compound targeting a chromatin-bound protein. Next, the proteins are cross-linked to DNA, and the associated DNA is purified and sequenced. In proof-of-concept studies in cultured human multiple myeloma (MM) cells, a biotinylated analog of the bromodomain inhibitor JQI mapped the compound to the same DNA regions as chromatin immunoprecipitation sequencing (ChIP-seq) assays with antibodies against bromodomain containing 4 (BRD4). Next steps include using Chem-seq to investigate drugs that target proteins that control transcription on a genome-wide scale and developing a more robust second-generation version of Chem-seq.

SciBX 7(2); doi:10.1038/scibx.2014.66
Published online Jan. 16, 2014

Patent application filed; licensed to Syros Pharmaceuticals Inc.

Anders, L. et al. Nat. Biotechnol.; published online Dec. 15, 2013;
Contact: James E. Bradner, Dana-Farber Cancer Institute, Boston, Mass.

Contact: Richard A. Young, Whitehead Institute for Biomedical Research, Cambridge, Mass.