Genome-wide localization of small molecules
A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide important...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2015
|
| Online Access: | http://hdl.handle.net/1721.1/96850 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1826214269313613824 |
|---|---|
| author | Anders, Lars Guenther, Matthew G. Qi, Jun Fan, Zi Peng Marineau, Jason J Rahl, Peter B Sigova, Alla A Smith, William B Lee, Tong Ihn Bradner, James E. Young, Richard A. Loven, Jakob |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Anders, Lars Guenther, Matthew G. Qi, Jun Fan, Zi Peng Marineau, Jason J Rahl, Peter B Sigova, Alla A Smith, William B Lee, Tong Ihn Bradner, James E. Young, Richard A. Loven, Jakob |
| author_sort | Anders, Lars |
| collection | MIT |
| description | A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods will be broadly useful to enhance understanding of therapeutic action and to characterize the specificity of chemical entities that interact with DNA or genome-associated proteins. |
| first_indexed | 2024-09-23T08:14:24Z |
| format | Article |
| id | mit-1721.1/96850 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:14:24Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/968502022-09-30T08:31:29Z Genome-wide localization of small molecules Anders, Lars Guenther, Matthew G. Qi, Jun Fan, Zi Peng Marineau, Jason J Rahl, Peter B Sigova, Alla A Smith, William B Lee, Tong Ihn Bradner, James E. Young, Richard A. Loven, Jakob Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Fan, Zi Peng Young, Richard A. A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods will be broadly useful to enhance understanding of therapeutic action and to characterize the specificity of chemical entities that interact with DNA or genome-associated proteins. National Institutes of Health (U.S.) (Grant HG002668) National Institutes of Health (U.S.) (Grant CA109901) National Institutes of Health (U.S.) (Grant CA146445) 2015-04-30T12:42:34Z 2015-04-30T12:42:34Z 2013-12 2013-10 Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 http://hdl.handle.net/1721.1/96850 Anders, Lars, Matthew G Guenther, Jun Qi, Zi Peng Fan, Jason J Marineau, Peter B Rahl, Jakob Loven, et al. “Genome-Wide Localization of Small Molecules.” Nature Biotechnology 32, no. 1 (December 15, 2013): 92–96. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1038/nbt.2776 Nature Biotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Anders, Lars Guenther, Matthew G. Qi, Jun Fan, Zi Peng Marineau, Jason J Rahl, Peter B Sigova, Alla A Smith, William B Lee, Tong Ihn Bradner, James E. Young, Richard A. Loven, Jakob Genome-wide localization of small molecules |
| title | Genome-wide localization of small molecules |
| title_full | Genome-wide localization of small molecules |
| title_fullStr | Genome-wide localization of small molecules |
| title_full_unstemmed | Genome-wide localization of small molecules |
| title_short | Genome-wide localization of small molecules |
| title_sort | genome wide localization of small molecules |
| url | http://hdl.handle.net/1721.1/96850 https://orcid.org/0000-0001-8855-8647 |
| work_keys_str_mv | AT anderslars genomewidelocalizationofsmallmolecules AT guenthermatthewg genomewidelocalizationofsmallmolecules AT qijun genomewidelocalizationofsmallmolecules AT fanzipeng genomewidelocalizationofsmallmolecules AT marineaujasonj genomewidelocalizationofsmallmolecules AT rahlpeterb genomewidelocalizationofsmallmolecules AT sigovaallaa genomewidelocalizationofsmallmolecules AT smithwilliamb genomewidelocalizationofsmallmolecules AT leetongihn genomewidelocalizationofsmallmolecules AT bradnerjamese genomewidelocalizationofsmallmolecules AT youngricharda genomewidelocalizationofsmallmolecules AT lovenjakob genomewidelocalizationofsmallmolecules |