The Role of Human Bromodomains in Chromatin Biology and Gene Transcription

Overview

Journal Curr Opin Drug Discov Devel

Specialties Chemistry
Pharmacology

Date 2009 Sep 9

PMID 19736624

Citations 157

Authors

Roberto Sanchez

Ming-Ming Zhou

Affiliations

Soon will be listed here.

Abstract

The acetylation of histone lysine is central to providing the dynamic regulation of chromatin-based gene transcription. The bromodomain (BRD), which is the conserved structural module in chromatin-associated proteins and histone acetyltranferases, is the sole protein domain known to recognize acetyl-lysine residues on proteins. Structural analyses of the recognition of lysine-acetylated peptides derived from histones and cellular proteins by BRDs have provided new insights into the differences between and unifying features of the selectivity that BRDs exhibit in binding biological ligands. Recent research has highlighted the importance of BRD/acetyl-lysine binding in orchestrating molecular interactions in chromatin biology and regulating gene transcription. These studies suggest that modulating BRD/acetyl-lysine interactions with small molecules may provide new opportunities for the control of gene expression in human health and disease.

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References

Huang H, Zhang J, Shen W, Wang X, Wu J, Wu J . Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails. BMC Struct Biol. 2007; 7:57. PMC: 2065866. DOI: 10.1186/1472-6807-7-57. View

VanDemark A, Kasten M, Ferris E, Heroux A, Hill C, Cairns B . Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation. Mol Cell. 2007; 27(5):817-28. PMC: 2788556. DOI: 10.1016/j.molcel.2007.08.018. View

Turner B . Histone acetylation as an epigenetic determinant of long-term transcriptional competence. Cell Mol Life Sci. 1998; 54(1):21-31. PMC: 11147230. DOI: 10.1007/s000180050122. View

Ottinger M, Christalla T, Nathan K, Brinkmann M, Viejo-Borbolla A, Schulz T . Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J Virol. 2006; 80(21):10772-86. PMC: 1641788. DOI: 10.1128/JVI.00804-06. View

Yokoyama S, Terwilliger T, Kuramitsu S, Moras D, Sussman J . RIKEN aids international structural genomics efforts. Nature. 2007; 445(7123):21. DOI: 10.1038/445021a. View

Mujtaba S, He Y, Zeng L, Farooq A, Carlson J, Ott M . Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. Mol Cell. 2002; 9(3):575-86. DOI: 10.1016/s1097-2765(02)00483-5. View

Zeng L, Zhou M . Bromodomain: an acetyl-lysine binding domain. FEBS Lett. 2002; 513(1):124-8. DOI: 10.1016/s0014-5793(01)03309-9. View

Dhalluin C, Carlson J, Zeng L, He C, Aggarwal A, Zhou M . Structure and ligand of a histone acetyltransferase bromodomain. Nature. 1999; 399(6735):491-6. DOI: 10.1038/20974. View

Neely K, Workman J . Histone acetylation and chromatin remodeling: which comes first?. Mol Genet Metab. 2002; 76(1):1-5. DOI: 10.1016/s1096-7192(02)00014-8. View

10.

Shen W, Xu C, Huang W, Zhang J, Carlson J, Tu X . Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails. Biochemistry. 2007; 46(8):2100-10. DOI: 10.1021/bi0611208. View

11.

Mujtaba S, Zeng L, Zhou M . Structure and acetyl-lysine recognition of the bromodomain. Oncogene. 2007; 26(37):5521-7. DOI: 10.1038/sj.onc.1210618. View

12.

Pal D, Evgrafov O, Tabares P, Zhang F, Durner M, Greenberg D . BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy. Am J Hum Genet. 2003; 73(2):261-70. PMC: 1180366. DOI: 10.1086/377006. View

13.

Zeng L, Zhang Q, Gerona-Navarro G, Moshkina N, Zhou M . Structural basis of site-specific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300. Structure. 2008; 16(4):643-52. PMC: 3339198. DOI: 10.1016/j.str.2008.01.010. View

14.

Ottinger M, Pliquet D, Christalla T, Frank R, Stewart J, Schulz T . The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. J Virol. 2009; 83(9):4423-34. PMC: 2668493. DOI: 10.1128/JVI.02274-08. View

15.

Zou J, Revenko A, Li L, Gemo A, Chen H . ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification. Proc Natl Acad Sci U S A. 2007; 104(46):18067-72. PMC: 2084297. DOI: 10.1073/pnas.0705814104. View

16.

Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, Sachchidanand . Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell. 2004; 13(2):251-63. DOI: 10.1016/s1097-2765(03)00528-8. View

17.

Berger S . Histone modifications in transcriptional regulation. Curr Opin Genet Dev. 2002; 12(2):142-8. DOI: 10.1016/s0959-437x(02)00279-4. View

18.

Singh M, Popowicz G, Krajewski M, Holak T . Structural ramification for acetyl-lysine recognition by the bromodomain of human BRG1 protein, a central ATPase of the SWI/SNF remodeling complex. Chembiochem. 2007; 8(11):1308-16. DOI: 10.1002/cbic.200600562. View

19.

Jacobson R, Ladurner A, King D, Tjian R . Structure and function of a human TAFII250 double bromodomain module. Science. 2000; 288(5470):1422-5. DOI: 10.1126/science.288.5470.1422. View

20.

Owen D, Ornaghi P, Yang J, Lowe N, Evans P, Ballario P . The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase gcn5p. EMBO J. 2000; 19(22):6141-9. PMC: 305837. DOI: 10.1093/emboj/19.22.6141. View