10. Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R,
Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK,
Lee K, Tarakhovsky A (2010) Suppression of inflammation by a synthetic histone mimic.
Nature 468(7327):1119–1123. https://doi.org/10.1038/nature09589
11. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M (2012) Epigenetic protein families: a
new frontier for drug discovery. Nat Rev Drug Discov 11(5):384–400. https://doi.org/10.1038/
nrd3674
12. Belkina AC, Denis GV (2012) BET domain co-regulators in obesity, inflammation and cancer.
Nat Rev Cancer 12(7):465–477. https://doi.org/10.1038/nrc3256
13. Brand M, Measures AM, Wilson BG, Cortopassi WA, Alexander R, Hoess M, Hewings DS,
Rooney TPC, Paton RS, Conway SJ (2015) Small molecule inhibitors of bromodomain-acetyllysine interactions. ACS Chem Biol 10(1):22–39. https://doi.org/10.1021/cb500996u
14. Zhang G, Smith SG, Zhou M-M (2015) Discovery of chemical inhibitors of human
bromodomains. Chem Rev 115(21):11625–11668. https://doi.org/10.1021/acs.chemrev.
5b00205
15. Chung C-W, Witherington J (2011) Progress in the discovery of small-molecule inhibitors of
bromodomain-histone interactions. J Biomol Screen 16(10):1170–1185. https://doi.org/10.
1177/1087057111421372
16. Zeng L, Li JM, Muller M, Yan S, Mujtaba S, Pan CF, Wang ZY, Zhou MM (2005) Selective
small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc
127(8):2376–2377. https://doi.org/10.1021/ja044885g
17. Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC, Kennison JA
(1992) Brahma - a regulator of drosophila homeotic genes structurally related to the yeast
transcriptional activator SNF2 SW12. Cell 68(3):561–572. https://doi.org/10.1016/0092-8674
(92)90191-e
18. Owen DJ, Ornaghi P, Yang JC, Lowe N, Evans PR, Ballario P, Neuhaus D, Filetici P,
Travers AA (2000) The structural basis for the recognition of acetylated histone H4 by the
bromodomain of histone acetyltransferase Gcn5p. EMBO J 19(22):6141–6149. https://doi.
org/10.1093/emboj/19.22.6141
19. Randazzo FM, Khavari P, Crabtree G, Tamkun J, Rossant J (1994) BRG1: a putative murine
homolog of the drosophila brahma gene, a homeotic gene regulator. Dev Biol 161(1):229–242.
https://doi.org/10.1006/dbio.1994.1023
20. Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I,
Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S (2012) Histone
recognition and large-scale structural analysis of the human bromodomain family. Cell
149(1):214–231. https://doi.org/10.1016/j.cell.2012.02.013
21. Jeanmougin F, Wurtz JM, LeDouarin B, Chambon P, Losson R (1997) The bromodomain
revisited. Trends Biochem Sci 22(5):151–153. https://doi.org/10.1016/s0968-0004(97)01042-6
22. Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM (1999) Structure and ligand
of a histone acetyltransferase bromodomain. Nature 399(6735):491–496
23. Jacobson RH, Ladurner AG, King DS, Tjian R (2000) Structure and function of a human
TAF(II)250 double bromodomain module. Science 288(5470):1422–1425. https://doi.org/10.
1126/science.288.5470.1422
24. Ornaghi P, Ballario P, Lena AM, Gonzalez A, Filetici P (1999) The bromodomain of Gcn5p
interacts in vitro with specific residues in the N terminus of histone H4. J Mol Biol 287(1):1–7.
https://doi.org/10.1006/jmbi.1999.2577
25. Hudson BP, Martinez-Yamout MA, Dyson HJ, Wright PE (2000) Solution structure and
acetyl-lysine binding activity of the GCN5 bromodomain. J Mol Biol 304(3):355–370.
https://doi.org/10.1006/jmbi.2000.4207
26. Vidler LR, Brown N, Knapp S, Hoelder S (2012) Druggability analysis and structural
classification of bromodomain acetyl-lysine binding sites. J Med Chem 55(17):7346–7359.
https://doi.org/10.1021/jm300346w
27. Liu J, Li F, Bao H, Jiang Y, Zhang S, Ma R, Gao J, Wu J, Ruan K (2017) The polar warhead of
a TRIM24 bromodomain inhibitor rearranges a water-mediated interaction network. FEBS J
284(7):1082–1095. https://doi.org/10.1111/febs.14041
328
W. C. K. Pomerantz et al.
Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK,
Lee K, Tarakhovsky A (2010) Suppression of inflammation by a synthetic histone mimic.
Nature 468(7327):1119–1123. https://doi.org/10.1038/nature09589
11. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M (2012) Epigenetic protein families: a
new frontier for drug discovery. Nat Rev Drug Discov 11(5):384–400. https://doi.org/10.1038/
nrd3674
12. Belkina AC, Denis GV (2012) BET domain co-regulators in obesity, inflammation and cancer.
Nat Rev Cancer 12(7):465–477. https://doi.org/10.1038/nrc3256
13. Brand M, Measures AM, Wilson BG, Cortopassi WA, Alexander R, Hoess M, Hewings DS,
Rooney TPC, Paton RS, Conway SJ (2015) Small molecule inhibitors of bromodomain-acetyllysine interactions. ACS Chem Biol 10(1):22–39. https://doi.org/10.1021/cb500996u
14. Zhang G, Smith SG, Zhou M-M (2015) Discovery of chemical inhibitors of human
bromodomains. Chem Rev 115(21):11625–11668. https://doi.org/10.1021/acs.chemrev.
5b00205
15. Chung C-W, Witherington J (2011) Progress in the discovery of small-molecule inhibitors of
bromodomain-histone interactions. J Biomol Screen 16(10):1170–1185. https://doi.org/10.
1177/1087057111421372
16. Zeng L, Li JM, Muller M, Yan S, Mujtaba S, Pan CF, Wang ZY, Zhou MM (2005) Selective
small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc
127(8):2376–2377. https://doi.org/10.1021/ja044885g
17. Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC, Kennison JA
(1992) Brahma - a regulator of drosophila homeotic genes structurally related to the yeast
transcriptional activator SNF2 SW12. Cell 68(3):561–572. https://doi.org/10.1016/0092-8674
(92)90191-e
18. Owen DJ, Ornaghi P, Yang JC, Lowe N, Evans PR, Ballario P, Neuhaus D, Filetici P,
Travers AA (2000) The structural basis for the recognition of acetylated histone H4 by the
bromodomain of histone acetyltransferase Gcn5p. EMBO J 19(22):6141–6149. https://doi.
org/10.1093/emboj/19.22.6141
19. Randazzo FM, Khavari P, Crabtree G, Tamkun J, Rossant J (1994) BRG1: a putative murine
homolog of the drosophila brahma gene, a homeotic gene regulator. Dev Biol 161(1):229–242.
https://doi.org/10.1006/dbio.1994.1023
20. Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I,
Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S (2012) Histone
recognition and large-scale structural analysis of the human bromodomain family. Cell
149(1):214–231. https://doi.org/10.1016/j.cell.2012.02.013
21. Jeanmougin F, Wurtz JM, LeDouarin B, Chambon P, Losson R (1997) The bromodomain
revisited. Trends Biochem Sci 22(5):151–153. https://doi.org/10.1016/s0968-0004(97)01042-6
22. Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM (1999) Structure and ligand
of a histone acetyltransferase bromodomain. Nature 399(6735):491–496
23. Jacobson RH, Ladurner AG, King DS, Tjian R (2000) Structure and function of a human
TAF(II)250 double bromodomain module. Science 288(5470):1422–1425. https://doi.org/10.
1126/science.288.5470.1422
24. Ornaghi P, Ballario P, Lena AM, Gonzalez A, Filetici P (1999) The bromodomain of Gcn5p
interacts in vitro with specific residues in the N terminus of histone H4. J Mol Biol 287(1):1–7.
https://doi.org/10.1006/jmbi.1999.2577
25. Hudson BP, Martinez-Yamout MA, Dyson HJ, Wright PE (2000) Solution structure and
acetyl-lysine binding activity of the GCN5 bromodomain. J Mol Biol 304(3):355–370.
https://doi.org/10.1006/jmbi.2000.4207
26. Vidler LR, Brown N, Knapp S, Hoelder S (2012) Druggability analysis and structural
classification of bromodomain acetyl-lysine binding sites. J Med Chem 55(17):7346–7359.
https://doi.org/10.1021/jm300346w
27. Liu J, Li F, Bao H, Jiang Y, Zhang S, Ma R, Gao J, Wu J, Ruan K (2017) The polar warhead of
a TRIM24 bromodomain inhibitor rearranges a water-mediated interaction network. FEBS J
284(7):1082–1095. https://doi.org/10.1111/febs.14041
328
W. C. K. Pomerantz et al.