Pooled ChIP-Seq Links Variation in Transcription Factor Binding to Complex Disease Risk
Copyright © 2016 Elsevier Inc. All rights reserved..
Cis-regulatory elements such as transcription factor (TF) binding sites can be identified genome-wide, but it remains far more challenging to pinpoint genetic variants affecting TF binding. Here, we introduce a pooling-based approach to mapping quantitative trait loci (QTLs) for molecular-level traits. Applying this to five TFs and a histone modification, we mapped thousands of cis-acting QTLs, with over 25-fold lower cost compared to standard QTL mapping. We found that single genetic variants frequently affect binding of multiple TFs, and CTCF can recruit all five TFs to its binding sites. These QTLs often affect local chromatin and transcription but can also influence long-range chromosomal contacts, demonstrating a role for natural genetic variation in chromosomal architecture. Thousands of these QTLs have been implicated in genome-wide association studies, providing candidate molecular mechanisms for many disease risk loci and suggesting that TF binding variation may underlie a large fraction of human phenotypic variation.
| Errataetall: |
CommentIn: Nat Rev Genet. 2016 Jun;17(6):317. - PMID 27140281 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:165 |
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| Enthalten in: |
Cell - 165(2016), 3 vom: 21. Apr., Seite 730-41 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tehranchi, Ashley K [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 13.12.2016 Date Revised 13.11.2018 published: Print-Electronic CommentIn: Nat Rev Genet. 2016 Jun;17(6):317. - PMID 27140281 Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2016.03.041 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM259488232 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 Elsevier Inc. All rights reserved. | ||
| 520 | |a Cis-regulatory elements such as transcription factor (TF) binding sites can be identified genome-wide, but it remains far more challenging to pinpoint genetic variants affecting TF binding. Here, we introduce a pooling-based approach to mapping quantitative trait loci (QTLs) for molecular-level traits. Applying this to five TFs and a histone modification, we mapped thousands of cis-acting QTLs, with over 25-fold lower cost compared to standard QTL mapping. We found that single genetic variants frequently affect binding of multiple TFs, and CTCF can recruit all five TFs to its binding sites. These QTLs often affect local chromatin and transcription but can also influence long-range chromosomal contacts, demonstrating a role for natural genetic variation in chromosomal architecture. Thousands of these QTLs have been implicated in genome-wide association studies, providing candidate molecular mechanisms for many disease risk loci and suggesting that TF binding variation may underlie a large fraction of human phenotypic variation | ||
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| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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| 700 | 1 | |a Myrthil, Marsha |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Trevor |e verfasserin |4 aut | |
| 700 | 1 | |a Hie, Brian L |e verfasserin |4 aut | |
| 700 | 1 | |a Golan, David |e verfasserin |4 aut | |
| 700 | 1 | |a Fraser, Hunter B |e verfasserin |4 aut | |
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