Nucleosome dynamics define transcriptional enhancers (original) (raw)

• Letter
• Published: 07 March 2010
• Clifford A Meyer1 na1,
• Hyunjin Shin1,
• Shannon T Bailey2,
• Gang Wei3,
• Qianben Wang2 nAff5,
• Yong Zhang1 nAff5,
• Kexin Xu2,
• Min Ni2,
• Mathieu Lupien2 nAff5,
• Piotr Mieczkowski4,
• Jason D Lieb4,
• Keji Zhao3,
• Myles Brown2 &
• …
• X Shirley Liu1

Nature Genetics volume 42, pages 343–347 (2010)Cite this article

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Abstract

Chromatin plays a central role in eukaryotic gene regulation. We performed genome-wide mapping of epigenetically marked nucleosomes to determine their position both near transcription start sites and at distal regulatory elements, including enhancers. In prostate cancer cells, where androgen receptor binds primarily to enhancers, we found that androgen treatment dismisses a central nucleosome present at androgen receptor binding sites that is flanked by a pair of marked nucleosomes. A new quantitative model built on the behavior of such nucleosome pairs correctly identified regions bound by the regulators of the immediate androgen response, including androgen receptor and FOXA1. More importantly, this model also correctly predicted previously unidentified binding sites for other transcription factors present after prolonged androgen stimulation, including OCT1 and NKX3-1. Therefore, quantitative modeling of enhancer structure provides a powerful predictive method to infer the identity of transcription factors involved in cellular responses to specific stimuli.

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Acknowledgements

This work was supported by grants from US National Institutes of Health (1R01 HG004069-02 to X.S.L., and 2P50 CA090381-06 to X.S.L. and M.B.), the Department of Defense (W81XWH-07-1-0037 to X.S.L.) and the Prostate Cancer Foundation (to M.B.).

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Author notes

1. Qianben Wang, Yong Zhang & Mathieu Lupien
   Present address: Present addresses: Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, Ohio, USA (Q.W.); School of Life Science and Technology, Tongji University, Shanghai, China (Y.Z.); and Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire, USA (M.L.).,
2. Housheng Hansen He and Clifford A Meyer: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, USA
   Housheng Hansen He, Clifford A Meyer, Hyunjin Shin, Yong Zhang & X Shirley Liu
2. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
   Housheng Hansen He, Shannon T Bailey, Qianben Wang, Kexin Xu, Min Ni, Mathieu Lupien & Myles Brown
3. Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
   Gang Wei & Keji Zhao
4. Department of Biology, Carolina Center for the Genome Sciences and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
   Piotr Mieczkowski & Jason D Lieb

Authors

1. Housheng Hansen He
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2. Clifford A Meyer
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3. Hyunjin Shin
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4. Shannon T Bailey
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5. Gang Wei
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6. Qianben Wang
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7. Yong Zhang
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8. Kexin Xu
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9. Min Ni
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10. Mathieu Lupien
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11. Piotr Mieczkowski
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12. Jason D Lieb
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13. Keji Zhao
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14. Myles Brown
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15. X Shirley Liu
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Contributions

H.H.H., C.A.M., K.Z., J.D.L., X.S.L. and M.B. designed the experiments. H.H.H., S.T.B., G.W., Q.W., K.X., M.N., M.L. and P.M. performed the experiments. C.A.M., H.H.H., H.S. and Y.Z. performed data analysis. C.A.M., H.H.H., X.S.L., M.B., J.D.L. and M.L. wrote the manuscript.

Corresponding authors

Correspondence toMyles Brown or X Shirley Liu.

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The authors declare no competing financial interests.

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He, H., Meyer, C., Shin, H. et al. Nucleosome dynamics define transcriptional enhancers.Nat Genet 42, 343–347 (2010). https://doi.org/10.1038/ng.545

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• Received: 02 October 2009
• Accepted: 09 February 2010
• Published: 07 March 2010
• Issue Date: April 2010
• DOI: https://doi.org/10.1038/ng.545

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