The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Structure and ligand of a histone acetyltransferase bromodomain
Abstract
Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, Lys-ac and Lys-cr may be interpreted differently, since they are recognized by distinct readers, in the bromodomain10 and Yeats domain11 respectively.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [10]
Citations
Cites
AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR
Laskowski, R., Rullmann, J. A., MacArthur, M., Kaptein, R., & Thornton, J. (1996) · Journal of Biomolecular NMR · doi:10.1007/bf00228148 · Cited by 5,502
X-PLOR Version 3.1: A System for X-ray Crystallography and NMR
Brünger, A. T. (1992) · Medical Entomology and Zoology · Cited by 3,424
The Anatomy and Taxonomy of Protein Structure
Richardson, J. S. (1981) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60520-3 · Cited by 3,378
NMR View: A computer program for the visualization and analysis of NMR data
Johnson, B. A., & Blevins, R. A. (1994) · Journal of Biomolecular NMR · doi:10.1007/bf00404272 · Cited by 3,093
The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., & Nakatani, Y. (1996) · Cell · doi:10.1016/s0092-8674(00)82001-2 · Cited by 2,952
Histone acetylation in chromatin structure and transcription
Grunstein, M. (1997) · Nature · doi:10.1038/38664 · Cited by 2,884
Protein modules and signalling networks
Pawson, T. (1995) · Nature · doi:10.1038/373573a0 · Cited by 2,420
The CBP co-activator is a histone acetyltransferase
Bannister, A. J., & Kouzarides, T. (1996) · Nature · doi:10.1038/384641a0 · Cited by 1,828
Brownell, J. E., Zhou, J., Ranalli, T. A., Kobayashi, R., Edmondson, D. G., Dent, S., & Allis, C. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81063-6 · Cited by 1,636
A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A
Yang, X., Ogryzko, V. V., Nishikawa, J., Howard, B. H., & Nakatani, Y. (1996) · Nature · doi:10.1038/382319a0 · Cited by 1,497
Chen, H., Lin, R. J., Schiltz, R. L., Chakravarti, D., Nash, A., Nagy, L., Privalsky, M. L., Nakatani, Y., & Evans, R. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80516-4 · Cited by 1,480
Carson, M. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891007240 · Cited by 809
Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines
Kuo, M.-H., Brownell, J. E., Sobel, R. E., Ranalli, T. A., Cook, R. G., Edmondson, D. G., Roth, S. Y., & Allis, C. D. (1996) · Nature · doi:10.1038/383269a0 · Cited by 596
Neri, D., Szyperski, T., Otting, G., Senn, H., & Kurt Wüthrich, A. (1989) · Biochemistry · doi:10.1021/bi00445a003 · Cited by 563
Brownell, J. E., & Allis, C. D. (1996) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(96)80048-7 · Cited by 534
Yamazaki, T., Lee, W., Arrowsmith, C. H., Muhandiram, D. R., & Kay, L. E. (1994) · Journal of the American Chemical Society · doi:10.1021/ja00105a005 · Cited by 499
The p300/CBP family: integrating signals with transcription factors and chromatin
Shiama, N. (1997) · Trends in Cell Biology · doi:10.1016/s0962-8924(97)01048-9 · Cited by 488
Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines
Otte, A. P. (1997) · UvA-DARE (University of Amsterdam) · Cited by 480
Differential Roles of p300 and PCAF Acetyltransferases in Muscle Differentiation
Puri, P., Sartorelli, V., Yang, X., Hamamori, Y., Ogryzko, V. V., Howard, B. H., Kedes, L., Wang, J. Y. J., Graessmann, A., Nakatani, Y., et al. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80005-2 · Cited by 419
The bromodomain: a conserved sequence found in human,Drosophilaand yeast proteins
Haynes, S. R., Dollard, C. A., Winston, F., Beck, S., Trowsdale, J., & Dawid, I. B. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.10.2603 · Cited by 387
Logan, T. M., Olejniczak, E. T., Xu, R., & Fesik, S. (1993) · Journal of Biomolecular NMR · doi:10.1007/bf00178264 · Cited by 301
Wolffe, A. P. (1997) · Nature · doi:10.1038/387016a0 · Cited by 282
Jeanmougin, F. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)01042-6 · Cited by 279
[11] Multidimensional heteronuclear nuclear magnetic resonance of proteins
Clore, G. M., & Gronenborn, A. M. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(94)39013-4 · Cited by 273
Ambiguous NOEs and automated NOE assignment
Nilges, M., & O’Donoghue, S. I. (1998) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/s0079-6565(97)00025-3 · Cited by 234
Structure of the Histone Acetyltransferase Hat1
Dutnall, R. N., Tafrov, S. T., Sternglanz, R., & Ramakrishnan, V. (1998) · Cell · doi:10.1016/s0092-8674(00)81584-6 · Cited by 224
Differential Use of CREB Binding Protein-Coactivator Complexes
Kurokawa, R., Kalafus, D., Ogliastro, M.-H., Kioussi, C., Xu, L., Torchia, J., Rosenfeld, M. G., & Glass, C. K. (1998) · Science · doi:10.1126/science.279.5351.700 · Cited by 211
Structural and functional diversity in 4-α-helical proteins
Weber, P. C., & Salemme, F. R. (1980) · Nature · doi:10.1038/287082a0 · Cited by 211
Topological distribution of four-alpha-helix bundles.
Presnell, S., & Cohen, F. E. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.17.6592 · Cited by 193
Georgakopoulos, T., Gounalaki, N., & Thireos, G. (1995) · Molecular and General Genetics MGG · doi:10.1007/bf00290718 · Cited by 36
Flagged first, then by citations
Research works printed but not linked: 1
- Nicholls, A., Bharadwj, R. & Honig, B. GRASP: Graphical representation and analysis of surface properties. Biophys. J. 64, 166–170 (1993).
Cited by
Sorted by citations
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756
The language of covalent histone modifications
Strahl, B. D., & Allis, C. D. (2000) · Nature · doi:10.1038/47412 · Cited by 8,679
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Bannister, A. J., Zegerman, P., Partridge, J. F., Miska, E. A., Thomas, J. O., Allshire, R. C., & Kouzarides, T. (2001) · Nature · doi:10.1038/35065138 · Cited by 2,903
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888
The molecular hallmarks of epigenetic control
Allis, C. D., & Jenuwein, T. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.59 · Cited by 2,809
Metadata
- Authors
- Dhalluin, C., Carlson, J. E., Zeng, L., He, C., Aggarwal, A. K., Zhou, M.-M., & Zhou, M.-M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Nature
- Published
- 1999-06
- Volume
- 399
- Issue
- 6735
- Pages
- 491-496
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1625510017
- Cited by
- 1,732
- References
- 30
- Citations by year
- 2026: 50 · 2025: 58 · 2024: 68 · 2023: 75 · 2022: 64 · 2021: 74 · 2020: 75 · 2019: 80 · 2018: 85 · 2017: 84 · 2016: 100 · 2015: 66 · 2014: 67 · 2013: 63 · 2012: 50
- FWCI
- 25.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- bromodomain, histone acetyltransferase, PCAF, protein structure, four-helix bundle, histone acetylation, transcriptional regulation, acetyl-CoA binding
- MeSH terms
- p300-CBP-Associated Factor, Acetyltransferases, Amino Acid Sequence, Escherichia coli, Ligands, Lysine, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Recombinant Proteins, Transcription Factors, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Bromine Compounds, Crystallography, X-Ray, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, p300-CBP Transcription Factors, Histone Acetyltransferases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
