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Oppermann, S. Mu¨ller, S. Sallan, C. Lathan, P. Rahl, R. Young, K. Lee and K. Shaw for discussions and sharing unpublished information; K. Agu, S. Johnston and L. Li for analytical chemistry support; J. Daley for flow cytometry support; T. Bowman, T. Caron, C. Marvin and S. Rodig for immunohistochemistry; and A. Bass for sharing cell lines. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. This research was supported by a Graduate Fellowship from the Chemistry-Biochemistry-Biology Interface Program at the University of Notre Dame, NIGMS T32-075762 (to Y.S.), the DF/HCC (to C.A.F. and J.E.B.), the National Institutes of Health, the Burroughs Wellcome Fund, and the Leukemia & Lymphoma Society (to J.E.B.). Author Contributions P.F., J.Q., S.K. and J.E.B. designed the study, analysed data and wrote the manuscript. P.F. and S.P. performed and analysed biophysical studies. J.Q. and J.E.B. designed JQ1 and established the synthetic routes. Y.S. and O.W. completed docking and molecular dynamics studies. O.F. performed and analysed DSF. S.M. and N.L.T. contributed biochemical assays.M.R.M.,M.P. and T.D.H. performed and analysed alpha-screen assays. W.B.S., M.J.C. and J.E.B. performed in vitro NMC studies and immunohistochemistry. E.M.M. performed flow cytometry studies. E.M.M. and N.W. performed proliferation studies. T.T.H.,M.J.C., C.A.F. and J.E.B. completed FRAP studies. M.R.M. and B.S. performed expression analysis. Y.W., A.L.C. and A.L.K. completed in vivo efficacy studies. T.K. and I.F. expressed and purified proteins. S.K. and J.E.B. supervised the research. Author Information Atomic coordinates and structure factors for the reported crystal structures have been deposited with the Protein Data Bank under accession codes 2OSS (BRD4(1)), 3MXF (BRD4(1)–(1)-JQ1) and 3ONI (BRD2(2)–(1)-JQ1). Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. Readers are welcome to comment on the online version of this article at www.nature.com/nature. Correspondence and requests for materials should be addressed to S.K. (stefan.knapp@sgc.ox.ac.uk) or J.E.B. (james_bradner@dfci.harvard.edu). ARTICLE RESEARCH 23/30 DECEMBER 2010 | VOL 468 | NATURE | 1073 ©2010 Macmillan Publishers Limited. All rights reserved