28. Fedorov O, Castex J, Tallant C, Owen DR, Martin S, Aldeghi M, Monteiro O,
Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D,
Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R,
Günther T, Knapp S, Müller S (2015) Selective targeting of the BRG/PB1 bromodomains
impairs embryonic and trophoblast stem cell maintenance. Sci Adv 1(10):e1500723. https://
doi.org/10.1126/sciadv.1500723
29. Crawford TD, Tsui V, Flynn EM, Wang S, Taylor AM, Cote A, Audia JE, Beresini MH,
Burdick DJ, Cummings R, Dakin LA, Duplessis M, Good AC, Hewitt MC, Huang H-R,
Jayaram H, Kiefer JR, Jiang Y, Murray J, Nasveschuk CG, Pardo E, Poy F, Romero FA,
Tang Y, Wang J, Xu Z, Zawadzke LE, Zhu X, Albrecht BK, Magnuson SR, Bellon S, Cochran
AG (2016) Diving into the water: inducible binding conformations for BRD4, TAF1(2),
BRD9, and CECR2 bromodomains. J Med Chem 59(11):5391–5402. https://doi.org/10.
1021/acs.jmedchem.6b00264
30. Divakaran A, Talluri SK, Ayoub AM, Mishra NK, Cui H, Widen JC, Berndt N, Zhu J-Y,
Carlson AS, Topczewski JJ, Schonbrunn EK, Harki DA, Pomerantz WCK (2018) Molecular
basis for the N-terminal bromodomain-and-extra-terminal-family selectivity of a dual kinase–
bromodomain inhibitor. J Med Chem 61(20):9316–9334. https://doi.org/10.1021/acs.
jmedchem.8b01248
31. Aldeghi M, Ross GA, Bodkin MJ, Essex JW, Knapp S, Biggin PC (2018) Large-scale analysis
of water stability in bromodomain binding pockets with grand canonical Monte Carlo.
Commun Chem 1(1):19. https://doi.org/10.1038/s42004-018-0019-x
32. Ruthenburg AJ, Li H, Patel DJ, Allis CD (2007) Multivalent engagement of chromatin
modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983–994. https://doi.
org/10.1038/nrm2298
33. Qin S, Jin L, Zhang J, Liu L, Ji P, Wu M, Wu J, Shi Y (2011) Recognition of unmodified
histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights
into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein
(MOZ) and MOZ-related factor (MORF). J Biol Chem 286(42):36944–36955. https://doi.
org/10.1074/jbc.M111.244400
34. Paz JC, Park S-H, Phillips N, Matsumura S, Tsai W-W, Kasper L, Brindle PK, Zhang G,
Zhou M-M, Wright PE, Montminy M (2014) Combinatorial regulation of a signal-dependent
activator by phosphorylation and acetylation. Proc Natl Acad Sci U S A 111
(48):17116–17121. https://doi.org/10.1073/pnas.1420389111
35. Miller TCR, Simon B, Rybin V, Groetsch H, Curtet S, Khochbin S, Carlomagno T, Mueller
CW (2016) A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. Nat Commun 7. https://doi.org/10.1038/
ncomms13855
36. Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, Sachchidanand, Sanchez R, Zeleznik-Le NJ,
Ronai Z, Zhou MM (2004) Structural mechanism of the bromodomain of the coactivator CBP
in p53 transcriptional activation. Mol Cell 13(2):251–263. https://doi.org/10.1016/s1097-2765
(03)00528-8
37. Mujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM (2002) Structural
basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. Mol Cell
9(3):575–586. https://doi.org/10.1016/s1097-2765(02)00483-5
38. Huang B, Yang X-D, Zhou M-M, Ozato K, Chen L-F (2009) Brd4 coactivates transcriptional
activation of NF-kappa B via specific binding to acetylated RelA. Mol Cell Biol
29(5):1375–1387. https://doi.org/10.1128/mcb.01365-08
39. Shi J, Wang YF, Zeng L, Wu YD, Deng J, Zhang Q, Lin YW, Li JL, Kang TB, Tao M,
Rusinova E, Zhang GT, Wang C, Zhu HN, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BHP
(2014) Disrupting the interaction of BRD4 with diacetylated twist suppresses tumorigenesis
in basal-like breast cancer. Cancer Cell 25(2):210–225. https://doi.org/10.1016/j.ccr.2014.
01.028
40. Asangani IA, Dommeti VL, Wang XJ, Malik R, Cieslik M, Yang RD, Escara-Wilke J,
Wilder-Romans K, Dhanireddy S, Engelke C, Iyer MK, Jing XJ, Wu YM, Cao XH, Qin
ZHS, Wang SM, Feng FY, Chinnaiyan AM (2014) Therapeutic targeting of BET
Applied Biophysics for Bromodomain Drug Discovery
329
Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D,
Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R,
Günther T, Knapp S, Müller S (2015) Selective targeting of the BRG/PB1 bromodomains
impairs embryonic and trophoblast stem cell maintenance. Sci Adv 1(10):e1500723. https://
doi.org/10.1126/sciadv.1500723
29. Crawford TD, Tsui V, Flynn EM, Wang S, Taylor AM, Cote A, Audia JE, Beresini MH,
Burdick DJ, Cummings R, Dakin LA, Duplessis M, Good AC, Hewitt MC, Huang H-R,
Jayaram H, Kiefer JR, Jiang Y, Murray J, Nasveschuk CG, Pardo E, Poy F, Romero FA,
Tang Y, Wang J, Xu Z, Zawadzke LE, Zhu X, Albrecht BK, Magnuson SR, Bellon S, Cochran
AG (2016) Diving into the water: inducible binding conformations for BRD4, TAF1(2),
BRD9, and CECR2 bromodomains. J Med Chem 59(11):5391–5402. https://doi.org/10.
1021/acs.jmedchem.6b00264
30. Divakaran A, Talluri SK, Ayoub AM, Mishra NK, Cui H, Widen JC, Berndt N, Zhu J-Y,
Carlson AS, Topczewski JJ, Schonbrunn EK, Harki DA, Pomerantz WCK (2018) Molecular
basis for the N-terminal bromodomain-and-extra-terminal-family selectivity of a dual kinase–
bromodomain inhibitor. J Med Chem 61(20):9316–9334. https://doi.org/10.1021/acs.
jmedchem.8b01248
31. Aldeghi M, Ross GA, Bodkin MJ, Essex JW, Knapp S, Biggin PC (2018) Large-scale analysis
of water stability in bromodomain binding pockets with grand canonical Monte Carlo.
Commun Chem 1(1):19. https://doi.org/10.1038/s42004-018-0019-x
32. Ruthenburg AJ, Li H, Patel DJ, Allis CD (2007) Multivalent engagement of chromatin
modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983–994. https://doi.
org/10.1038/nrm2298
33. Qin S, Jin L, Zhang J, Liu L, Ji P, Wu M, Wu J, Shi Y (2011) Recognition of unmodified
histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights
into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein
(MOZ) and MOZ-related factor (MORF). J Biol Chem 286(42):36944–36955. https://doi.
org/10.1074/jbc.M111.244400
34. Paz JC, Park S-H, Phillips N, Matsumura S, Tsai W-W, Kasper L, Brindle PK, Zhang G,
Zhou M-M, Wright PE, Montminy M (2014) Combinatorial regulation of a signal-dependent
activator by phosphorylation and acetylation. Proc Natl Acad Sci U S A 111
(48):17116–17121. https://doi.org/10.1073/pnas.1420389111
35. Miller TCR, Simon B, Rybin V, Groetsch H, Curtet S, Khochbin S, Carlomagno T, Mueller
CW (2016) A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT. Nat Commun 7. https://doi.org/10.1038/
ncomms13855
36. Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, Sachchidanand, Sanchez R, Zeleznik-Le NJ,
Ronai Z, Zhou MM (2004) Structural mechanism of the bromodomain of the coactivator CBP
in p53 transcriptional activation. Mol Cell 13(2):251–263. https://doi.org/10.1016/s1097-2765
(03)00528-8
37. Mujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM (2002) Structural
basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. Mol Cell
9(3):575–586. https://doi.org/10.1016/s1097-2765(02)00483-5
38. Huang B, Yang X-D, Zhou M-M, Ozato K, Chen L-F (2009) Brd4 coactivates transcriptional
activation of NF-kappa B via specific binding to acetylated RelA. Mol Cell Biol
29(5):1375–1387. https://doi.org/10.1128/mcb.01365-08
39. Shi J, Wang YF, Zeng L, Wu YD, Deng J, Zhang Q, Lin YW, Li JL, Kang TB, Tao M,
Rusinova E, Zhang GT, Wang C, Zhu HN, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BHP
(2014) Disrupting the interaction of BRD4 with diacetylated twist suppresses tumorigenesis
in basal-like breast cancer. Cancer Cell 25(2):210–225. https://doi.org/10.1016/j.ccr.2014.
01.028
40. Asangani IA, Dommeti VL, Wang XJ, Malik R, Cieslik M, Yang RD, Escara-Wilke J,
Wilder-Romans K, Dhanireddy S, Engelke C, Iyer MK, Jing XJ, Wu YM, Cao XH, Qin
ZHS, Wang SM, Feng FY, Chinnaiyan AM (2014) Therapeutic targeting of BET
Applied Biophysics for Bromodomain Drug Discovery
329