Histone acetylation regulates chromatin accessibility: Role of H4K16 in inter-nucleosome interaction
Open accessAbstract
The N-terminal tail of histone H4 is an indispensable mediator for inter-nucleosome interaction, which is required for chromatin fiber condensation. H4K16 acetylation (H4K16Ac) activates gene transcription by influencing both chromatin structure and interplay with nonhistone proteins. To understand the influence of H4K16Ac on inter-nucleosome interaction, we performed a simulation study for the H4 tail in the context of two nucleosomes in neighboring unit cells in the crystal structure. The binding conformation of H4 tail with/without K16Ac was sampled by replica exchange with solute tempering, and the free energy landscape was explored by metadynamics. The results indicate two important features of H4K16: 1) it is the first button to anchor the H4 tail on the adjacent nucleosome; and 2) it is the only acetylation site interacting with the acidic patch. H4K16Ac disrupts the electrostatic interactions of K16, weakens H4 tail-acidic patch binding, and significantly increases H4 tail conformation diversity. Our study suggests that H4K16Ac directly reduces the inter-nucleosome interaction mediated by the H4 tail, which might further encourage the binding of nonhistone proteins on the acidic patch.
Integrity signals
Registry
Cites
Statistics
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?
Under physiological conditions, the balance between HDAC activity and histone acetylation shapes chromatin accessibility and thereby influences gene expression in the nervous system.
“Under physiological conditions, the balance between HDAC activity and histone acetylation shapes chromatin accessibility and thereby influences gene expression in the nervous system (Zhang et al., 2017).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Zhang et al., 2017
Cites
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 29,588 · see citing works
GROMACS: Fast, flexible, and free
van der Spoel, D., Lindahl, E. R., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. C. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20291 · Cited by 19,187 · see citing works
LINCS: A linear constraint solver for molecular simulations
Hess, B., Bekker, H., Berendsen, H. J. C., & Fraaije, J. G. E. M. (1997) · Journal of Computational Chemistry · doi:10.1002/(sici)1096-987x(199709)18:12 · Cited by 18,369 · see citing works
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation
Hess, B., Kutzner, C., van der Spoel, D., & Lindahl, E. R. (2008) · Journal of Chemical Theory and Computation · doi:10.1021/ct700301q · Cited by 15,830 · see citing works
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz, K. M., Ferguson, D. M., Spellmeyer, D. C., Fox, T., Caldwell, J. W., & Kollman, P. A. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00124a002 · Cited by 13,111 · see citing works
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466 · see citing works
Bayly, C. I., Cieplak, P., Cornell, W. D., & Kollman, P. A. (1993) · The Journal of Physical Chemistry · doi:10.1021/j100142a004 · Cited by 8,152 · see citing works
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit
Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., Shirts, M. R., Smith, J. C., Kasson, P. M., van der Spoel, D., et al. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt055 · Cited by 7,493 · see citing works
Comparison of multiple Amber force fields and development of improved protein backbone parameters
Horn̆ák, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A. E., & Simmerling, C. L. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21123 · Cited by 6,903 · see citing works
Laio, A., & Parrinello, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202427399 · Cited by 5,626 · see citing works
Automatic atom type and bond type perception in molecular mechanical calculations
Wang, J., Wang, W., Kollman, P. A., & Case, D. A. (2006) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2005.12.005 · Cited by 5,517 · see citing works
Replica-exchange molecular dynamics method for protein folding
Sugita, Y., & Okamoto, Y. (1999) · Chemical Physics Letters · doi:10.1016/s0009-2614(99)01123-9 · Cited by 4,499 · see citing works
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation
Hess, B. (2007) · Journal of Chemical Theory and Computation · doi:10.1021/ct700200b · Cited by 4,020 · see citing works
PLUMED 2: New feathers for an old bird
Tribello, G. A., Bonomi, M., Branduardi, D., Camilloni, C., & Bussi, G. (2013) · Computer Physics Communications · doi:10.1016/j.cpc.2013.09.018 · Cited by 3,427 · see citing works
Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
Barducci, A., Bussi, G., & Parrinello, M. (2008) · Physical Review Letters · doi:10.1103/physrevlett.100.020603 · Cited by 3,184 · see citing works
Onufriev, A., Bashford, D., & Case, D. A. (2004) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.20033 · Cited by 2,507 · see citing works
Peptide Folding: When Simulation Meets Experiment
Daura, X., Gademann, K., Jaun, B., Seebàch, D., van Gunsteren, W. F., & Mark, A. E. (1999) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19990115)38:1/2 · Cited by 2,059 · see citing works
Fraga, M. F., Ballestar, E., Villar‐Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C. E., Ropero, S., Petrie, K. R., et al. (2005) · Nature Genetics · doi:10.1038/ng1531 · Cited by 1,926 · see citing works
PLUMED: A portable plugin for free-energy calculations with molecular dynamics
Bonomi, M., Branduardi, D., Bussi, G., Camilloni, C., Provasi, D., Raiteri, P., Donadio, D., Marinelli, F., Pietrucci, F., Broglia, R. A., et al. (2009) · Computer Physics Communications · doi:10.1016/j.cpc.2009.05.011 · Cited by 1,890 · see citing works
Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions
Shogren‐Knaak, M. A., Ishii, H., Sun, J.-M., Pazin, M. J., Davie, J., & Peterson, C. L. (2006) · Science · doi:10.1126/science.1124000 · Cited by 1,876 · see citing works
Laio, A., & Gervasio, F. L. (2008) · Reports on Progress in Physics · doi:10.1088/0034-4885/71/12/126601 · Cited by 1,619 · see citing works
Solvent Mediated Interactions in the Structure of the Nucleosome Core Particle at 1.9Å Resolution
Davey, C. A., Sargent, D. F., Luger, K., Mäder, A. W., & Richmond, T. J. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00386-8 · Cited by 1,490 · see citing works
X-ray structure of a tetranucleosome and its implications for the chromatin fibre
Schalch, T., Duda, S., Sargent, D. F., & Richmond, T. J. (2005) · Nature · doi:10.1038/nature03686 · Cited by 839 · see citing works
Fukunishi, H., Watanabe, O., & Takada, S. (2002) · The Journal of Chemical Physics · doi:10.1063/1.1472510 · Cited by 713 · see citing works
Replica exchange with solute tempering: a method for sampling biological systems in explicit water.
Liu, P., Kim, B., Friesner, R., & Berne, B. (2005) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0506346102 · Cited by 698 · see citing works
Nucleosome Arrays Reveal the Two-Start Organization of the Chromatin Fiber
Dorigo, B., Schalch, T., Kulangara, A., Duda, S., Schroeder, R. R., & Richmond, T. J. (2004) · Science · doi:10.1126/science.1103124 · Cited by 562 · see citing works
Chromatin Fiber Folding: Requirement for the Histone H4 N-terminal Tail
Dorigo, B., Schalch, T., Bystricky, K., & Richmond, T. J. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00025-1 · Cited by 527 · see citing works
Akhtar, A., & Becker, P. B. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80431-1 · Cited by 482 · see citing works
Molecular Dynamics Simulations of Nucleic Acids with a Generalized Born Solvation Model
Tsui, V., & Case, D. A. (2000) · Journal of the American Chemical Society · doi:10.1021/ja9939385 · Cited by 433 · see citing works
Genomic characterization reveals a simple histone H4 acetylation code
Dion, M. F., Altschuler, S. J., Wu, L. F., & Rando, O. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500136102 · Cited by 395 · see citing works
Role of histone acetylation in the control of gene expression
Verdone, L., Caserta, M., & Mauro, E. D. (2005) · Biochemistry and Cell Biology · doi:10.1139/o05-041 · Cited by 391 · see citing works
30 nm Chromatin Fibre Decompaction Requires both H4-K16 Acetylation and Linker Histone Eviction
Robinson, P. J. J., An, W., Routh, A. L., Martino, F., Chapman, L., Roeder, R. G., & Rhodes, D. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.04.050 · Cited by 311 · see citing works
Hamiltonian replica exchange in GROMACS: a flexible implementation
Bussi, G. (2013) · Molecular Physics · doi:10.1080/00268976.2013.824126 · Cited by 277 · see citing works
The role of the nucleosome acidic patch in modulating higher order chromatin structure
Kalashnikova, A. A., Porter-Goff, M. E., Muthurajan, U. M., Luger, K., & Hansen, J. C. (2013) · Journal of The Royal Society Interface · doi:10.1098/rsif.2012.1022 · Cited by 271 · see citing works
Krishnan, V., Chow, M. Z. Y., Wang, Z., Zhang, L., Liu, B., Liu, X., & Zhou, Z. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102789108 · Cited by 236 · see citing works
The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association
Allahverdi, A., Yang, R., Korolev, N., Fan, Y.-P., Davey, C. A., Liu, C., & Nordenskiöld, L. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq900 · Cited by 226 · see citing works
Taylor, G. C. A., Eskeland, R., Hekimoglu-Balkan, B., Pradeepa, M. M., & Bickmore, W. A. (2013) · Genome Research · doi:10.1101/gr.155028.113 · Cited by 191 · see citing works
Arya, G., & Schlick, T. (2009) · The Journal of Physical Chemistry A · doi:10.1021/jp810375d · Cited by 180 · see citing works
Collepardo‐Guevara, R., Portella, G., Vendruscolo, M., Frenkel, D., Tamar Schlick, A., & Orozco, M. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b04086 · Cited by 174 · see citing works
Acetylation Increases the α-Helical Content of the Histone Tails of the Nucleosome
Wang, X., Moore, S. C., Laszckzak, M., & Ausió, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004998200 · Cited by 156 · see citing works
On easy implementation of a variant of the replica exchange with solute tempering in GROMACS
Terakawa, T., Kameda, T., & Takada, S. (2010) · Journal of Computational Chemistry · doi:10.1002/jcc.21703 · Cited by 137 · see citing works
Pepenella, S., Murphy, K. J., & Hayes, J. J. (2013) · Chromosoma · doi:10.1007/s00412-013-0435-8 · Cited by 133 · see citing works
A dual role of H4K16 acetylation in the establishment of yeast silent chromatin
Oppikofer, M., Kueng, S., Martino, F., Soeroes, S., Hancock, S. M., Chin, J. W., Fischle, W., & Gasser, S. M. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.170 · Cited by 100 · see citing works
The Role of Histone Tails in the Nucleosome: A Computational Study
Erler, J., Zhang, R., Petridis, L., et al. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.10.065 · Cited by 85 · see citing works
Self-citationWakamori, M., Fujii, Y., Suka, N., et al. (2015) · Scientific Reports · doi:10.1038/srep17204 · Cited by 85 · see citing works
Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation
Potoyan, D. A., & Papoian, G. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201805109 · Cited by 82 · see citing works
Zheng, C. Y., & Hayes, J. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302817200 · Cited by 78 · see citing works
Influence of Histone Tails and H4 Tail Acetylations on Nucleosome–Nucleosome Interactions
Liu, Y., Lu, C., Ye, Y., Fan, Y.-P., Yang, R., Liu, C., Korolev, N., & Nordenskiöld, L. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.10.031 · Cited by 76 · see citing works
Sinha, D., & Shogren‐Knaak, M. A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091298 · Cited by 74 · see citing works
Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation
Yang, D., & Arya, G. (2010) · Physical Chemistry Chemical Physics · doi:10.1039/c0cp01487g · Cited by 64 · see citing works
Winogradoff, D. N., Echeverria, I., Potoyan, D. A., & Papoian, G. A. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b00235 · Cited by 64 · see citing works
Pepenella, S., Murphy, K. J., & Hayes, J. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.595140 · Cited by 41 · see citing works
Saurabh, S., Glaser, M. A., Lansac, Y., & Maiti, P. K. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b11863 · Cited by 36 · see citing works
Elucidating Internucleosome Interactions and the Roles of Histone Tails
Howell, S. C., Andresen, K., Jimenez‐Useche, I., et al. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2013.05.021 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Role of histone deacetylases and their inhibitors in neurological diseases
Zhang, L.-Y., Zhang, S.-Y., Wen, R., Zhang, T.-N., & Yang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107410 · Cited by 84 · see citing works
Lv, L.-Z., Wang, Z.-D., Ren, J.-J., Li, L.-H., Liu, X.-B., Li, J.-L., Zhu, H., Jiang, B., Han, Y.-P., Zhou, X.-M., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1722453 · Cited by 7 · see citing works
- Authors
- Zhang, R., Erler, J., & Langowski, J.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Langowski, Jörg
- Venue
- Biophysical Journal
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 112
- Issue
- 3
- Pages
- 450-459
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC5300776
- OpenAlex
- W2560656057
- Cited by
- 142
- References
- 55
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 12 · 2023: 8 · 2022: 14 · 2021: 14 · 2020: 23 · 2019: 26 · 2018: 16 · 2017: 5
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HGS MathComp
- DFG (GSC 220)
- Boehringer Ingelheim Fonds
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- histone acetylation, chromatin accessibility, nucleosome, acidic patch, electrostatic interactions, free energy landscape
- MeSH terms
- Acetylation, Histones, Hydrogen-Ion Concentration, Lysine, Models, Molecular, Nucleic Acid Conformation, Nucleosomes, Protein Structure, Quaternary, Protein Multimerization, Protein Stability
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
