Thursday, January 16, 2014
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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.
Published online Jan. 16, 2014
Patent application filed;
licensed to Syros
Anders, L. et al. Nat.
Biotechnol.; published online Dec. 15, 2013;
Contact: James E. Bradner, Dana-Farber Cancer Institute,
Contact: Richard A. Young, Whitehead Institute for
Biomedical Research, Cambridge, Mass.
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