Regulation of nucleosome dynamics by histone modifications
Abstract
Chromatin is a dynamic structure that must respond to myriad stimuli to regulate access to DNA, and chemical modification of histones is a major means by which the cell modulates nucleosome mobility and turnover. Histone modifications are linked to essentially every cellular process requiring DNA access, including transcription, replication and repair. Here we consider properties of the major types of histone modification in the context of their associated biological processes to view them in light of the cellular mechanisms that regulate nucleosome dynamics.
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Histones enter nucleosome formation and proper DNA wrapping after the S phase of cell cycle.
“histones enter in nucleosome formation and proper DNA wrapping after the S phase of cell cycle [65]”
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Activator-Induced Spread of Poly(ADP-Ribose) Polymerase Promotes Nucleosome Loss at Hsp70
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Epigenetic inheritance: uncontested
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Expansion of the Lysine Acylation Landscape
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Histone H3 Lysine 36 Methylation Targets the Isw1b Remodeling Complex to Chromatin
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Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling
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Codependency of H2B monoubiquitination and nucleosome reassembly on Chd1Preprint
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Blocking by Histones of Accessibility to DNA in Chromatin: Addition of Histones
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Regulation of type I interferon responses
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“org/publicdomain/ze The structure of chromatin regulates the accessibility of genes for the transcriptional machinery, and is thus an integral part of regulated gene expression in stress responses and development [8, 9].”
BackgroundGetting up to speed with transcription elongation by RNA polymerase II
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Understanding nucleosome dynamics and their links to gene expression and DNA replication
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Release and activity of histone in diseases
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“Moreover, histone post-translational modifications (PTMs) have a critical role in the regulation of nucleosome dynamics and multiple DNA-associated processes such as transcription, replication, and repair.(2,3) Various histone PTMs and their combinations lead to the generation of the histone code hypothesis and epigen…”
BackgroundTargeting histone methyltransferases and demethylases in clinical trials for cancer therapy
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BackgroundNucleosomes Are Context-Specific, H2A.Z-Modulated Barriers to RNA Polymerase
Weber, C. M., Ramachandran, S., & Henikoff, S. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.014 · Cited by 386 · see citing works
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Mitochondria and Epigenetics – Crosstalk in Homeostasis and Stress
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Chromatin and nucleosome dynamics in DNA damage and repairPreprint
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Inside HDACs with more selective HDAC inhibitors
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“[88] have identified by screening N-[1,3,4]thiadiazol-2-yl an d N-thiazol-2yl sulfonamide groups as promising ZBG, with probabl y etter physicochemical properties than hydroxamic acids as demonstrated by their current clinical applications .”
BackgroundWhat are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory
Steffen, P. A., & Ringrose, L. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3789 · Cited by 318 · see citing works
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Chromatin replication and epigenetic cell memory
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Transgenerational developmental programming
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“A number of possible modifications to histones are possible, including methylation, phosphorylation and acetylation, all of which can change the interaction between histones and DNA to alter gene expression (Zentner and Henikoff, 2013).”
BackgroundEpigenetics and Allergy: from Basic Mechanisms to Clinical Applications
Potaczek, D. P., Harb, H., Michel, S., Alhamwe, B. A., Renz, H. E., & Tost, J. (2017) · Epigenomics · doi:10.2217/epi-2016-0162 · Cited by 280 · see citing works
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“Amino-terminal tails of core histones protrude from the nucleosome and are subject to a plethora of posttranslational modifications (PTMs), which regulate almost all cellular processes requiring access to DNA, in particular gene transcription (Zentner and Henikoff, 2013).”
BackgroundTargeting Metalloenzymes for Therapeutic Intervention
Chen, A. Y., Adamek, R. N., Dick, B. L., Credille, C. V., Morrison, C. N., & Cohen, S. M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00201 · Cited by 277 · see citing works
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“…promoters with differential H3K9ac for both D5/ND and D7/ND was the ABRE consensus motif for the AREB1 TF. Charron et al., 2009; Zhou et al., 2010; Li et al., 2011; Zentner and Henikoff, 2013), combinations showing hUP-gUP and hDN-gDN are most likely to represent direct effects on gene expression.”
BackgroundJacquet, K., Fradet‐Turcotte, A., Avvakumov, N., Lambert, J., Lopez‐Roques, C., PANDITA, R. K., Paquet, É. R., Herst, P. M., Gingras, A., Pandita, T. K., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.031 · Cited by 260 · see citing works
“Histone post-translational modifications (PTMs) act as key regulators of chromatin organization, mainly by serving as docking sites for chromatin-binding factors (Zentner and Henikoff, 2013).”
BackgroundXavier, M. J., Roman, S. D., Aitken, R. J., & Nixon, B. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz017 · Cited by 258 · see citing works
Chromatin dynamics: Interplay between remodeling enzymes and histone modifications
Swygert, S. G., & Peterson, C. L. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.02.013 · Cited by 257 · see citing works
“Common modifications include lysine acetylation, the mono-, di-, or trimethylation of lysines, mono- or di-methylation of arginines, the phosphorylation of serines, threonines, or tyrosines, as well as lysine ubiquitylation and SUMOylation [6].”
BackgroundMethodInfluentialEZH2-Targeted Therapies in Cancer: Hype or a Reality
Eich, M., Athar, M., Ferguson, J. E., & Varambally, S. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2147 · Cited by 246 · see citing works
“These enzymes catalyze a variety of posttranslational modifications including methylation, acetylation, phosphorylation, ubiquitination, and sumoylation (12).”
BackgroundBromodomains: Structure, function and pharmacology of inhibition
Ferri, E., Petosa, C., & McKenna, C. E. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.12.005 · Cited by 238 · see citing works
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“Zentner and Henikoff (2013) suggested histone modifications such as methylation, phosphorylation and acetylation can alter DNA access in such a way that that affects transcription, replication and repair.”
BackgroundA Macrohistone Variant Links Dynamic Chromatin Compaction to BRCA1-Dependent Genome Maintenance
Khurana, S., Kruhlak, M. J., Kim, J., Tran, A. D., Liu, J., Nyswaner, K., Shi, L., Jailwala, P., Sung, M.-H., Hakim, O., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.024 · Cited by 220 · see citing works
“Chromatin reorganization generally involves the covalent modification of histone tails as well as histone (variant) exchange, which together affect nucleosome density and DNA accessibility (Zentner and Henikoff, 2013).”
BackgroundRamazi, S., Allahverdi, A., & Zahiri, J. (2020) · Journal of Biosciences · doi:10.1007/s12038-020-00099-2 · Cited by 219 · see citing works
“This modification is known as one of the reversible types of PTMs in core histones and as well as linker histone H1 (Burzio et al. 1979; Messner and Hottiger 2011; van der Heden et al. 2010; Zentner and Henikoff 2013).”
BackgroundInfluentialUndercover: gene control by metabolites and metabolic enzymesPreprint
van der Knaap, J. A., & Verrijzer, C. P. (2016) · Genes & Development · doi:10.1101/gad.289140.116 · Cited by 213 · see citing works
“Transcriptional activity is intimately associated with specific histone modifications (Patel and Wang 2013; Zentner and Henikoff 2013; Swygert and Peterson 2014; Allis and Jenuwein 2016).”
BackgroundArabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling
Brzezinka, K., Altmann, S., Czesnick, H., Nicolas, P., Górka, M., Benke, E., Kabelitz, T., Jähne, F., Graf, A., Kappel, C., et al. (2016) · eLife · doi:10.7554/elife.17061 · Cited by 206 · see citing works
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“Intriguingly, in addition to methylation and acetylation, histones can be modified by the addition of other chemical moieties including phosphorylation, ubiquitination, sumoylation and ADP-ribosylation (116).”
BackgroundAlternative Splicing and Protein Diversity: Plants Versus Animals
Chaudhary, S., Khokhar, W., Jabre, I., Reddy, A. S. N., Byrne, L. J., Wilson, C. M., & Syed, N. H. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2019.00708 · Cited by 204 · see citing works
Targeting histone lysine demethylases — Progress, challenges, and the future
Thinnes, C. C., England, K. S., Kawamura, A., Chowdhury, R., Schofield, C. J., & Hopkinson, R. J. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.05.009 · Cited by 195 · see citing works
“These modifications, together with other factors, are proposed to substantially contribute to the regulation of gene expression in a context-dependent manner, in part by affecting the accessibility of DNAsequences for transcription [1–3].”
BackgroundDangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancerPreprint
Bracken, A. P., Brien, G. L., & Verrijzer, C. P. (2019) · Genes & Development · doi:10.1101/gad.326066.119 · Cited by 192 · see citing works
“In addition, chromatin state is regulated through a plethora of posttranslationalmodifications, in particular of the unstructured N-terminal histone tails that protrude from the nucleosome (Zentner and Henikoff 2013; Allis and Jenuwein 2016).”
BackgroundTargeting histone lysine methylation in cancer
McGrath, J. P., & Trojer, P. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.01.002 · Cited by 188 · see citing works
Establishment and Functions of DNA Methylation in the Germline
Stewart-Morgan, K. R., Veselovska, L., & Kelsey, G. (2016) · Epigenomics · doi:10.2217/epi-2016-0056 · Cited by 185 · see citing works
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Mechanosensing and Mechanoregulation of Endothelial Cell Functions
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Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics
Bao, X., Liu, Z., Zhang, W., Gladysz, K., Fung, Y. M. E., Tian, G., Xiong, Y., Wong, J. W. H., Yuen, K. W. Y., & Li, X. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.018 · Cited by 164 · see citing works
Epigenetics in Insects: Genome Regulation and the Generation of Phenotypic Diversity
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“This increases the accessibility of underlying DNA or facilitates the movement of the nucleosome along the DNA, both of which allow for the binding of DNA-binding factors (36, 150, 151).”
BackgroundLocal Determinants of the Mutational Landscape of the Human Genome
González-Pérez, A., Sabarinathan, R., & López-Bigas, N. (2019) · Cell · doi:10.1016/j.cell.2019.02.051 · Cited by 162 · see citing works
Mendelian Disorders of the Epigenetic Machinery: Tipping the Balance of Chromatin States
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“In general, acetylation of histones by histone acetyltransferases is associated with active gene expression, and deacetylated histones (mediated by histone deacetylases) tend to be present in transcriptionally silent regions (137).”
InfluentialIL-21 induces IL-22 production in CD4+ T cells
Yeste, A., Mascanfroni, I. D., Nadeau, M., Burns, E. J., Tukpah, A.-M. C., Santiago, A. F., Wu, C., Patel, B., Kumar, D., & Quintana, F. J. (2014) · Nature Communications · doi:10.1038/ncomms4753 · Cited by 157 · see citing works
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Molecular mechanisms of plant tolerance to heat stress: current landscape and future perspectives
Haider, S., Iqbal, J., Naseer, S., Yaseen, T., Shaukat, M., Bibi, H., Ahmad, Y., Daud, H., Abbasi, N. L., & Mahmood, T. (2021) · Plant Cell Reports · doi:10.1007/s00299-021-02696-3 · Cited by 156 · see citing works
“The chromatin structure and dynamics regulate gene expression by controlling the accessibility of genomic DNA sequence for the general transcriptional machinery, in response to development and stress event (Struhl and Segal 2013; Zentner and Henikoff 2013).”
BackgroundOncometabolites‐driven tumorigenesis: From genetics to targeted therapy
Morin, A., Letouzé, É., Gimenez‐Roqueplo, A., & Favier, J. (2014) · International Journal of Cancer · doi:10.1002/ijc.29080 · Cited by 150 · see citing works
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“The titration of DNA-bound H3(1-10)K4me3 into (15)N382 PHD yielded very similar CSPs as were observed upon titration of H3(1-10)K4me3 383 alone (Figure 6A).”
InfluentialRoles of Histone Deacetylases and Inhibitors in Anticancer Therapy
Verza, F. A., Das, U., Fachin, A. L., Dimmock, J. R., & Marins, M. (2020) · Cancers · doi:10.3390/cancers12061664 · Cited by 147 · see citing works
“This weakened binding can facilitate the action of transcription factors in this altered region, inducing or repressing gene transcription [13].”
BackgroundHuang, H., Nace, G., McDonald, K.-A., Tai, S., Klune, J. R., Rosborough, B. R., Ding, Q., Loughran, P., Zhu, X., Beer–Stolz, D., et al. (2013) · Hepatology · doi:10.1002/hep.26976 · Cited by 146 · see citing works
“X has been shown to be phosphorylated in response to DNA damage, serving as a marker of DNA damage.(18) We found that loss of HMGB1 within hepatocytes resulted in a”
BackgroundGaarenstroom, T., & Hill, C. S. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.01.009 · Cited by 146 · see citing works
“High hisone turnover in combination with the neutralization of positive harge resulting from the acetylation, likely aid in the creation of ore accessible chromatin [8,9].”
BackgroundStress memory responses and seed priming correlate with drought tolerance in plants: an overview
Liu, X., Quan, W., & Bartels, D. (2022) · Planta · doi:10.1007/s00425-022-03828-z · Cited by 148 · see citing works
“Histone methylation predominantly occurs on lysine and arginine residues including mono-methylation, di-methylation, or tri-methylation (Bannister and Kouzarides 2011; Zentner and Henikoff 2013).”
BackgroundZhong, H.-J., Lu, L., Leung, K.-H., Wong, C. C. L., Peng, C., Yan, S.-C., Ma, D.-L., Cai, Z., David Wang, H.-M., & Leung, C.-H. (2015) · Chemical Science · doi:10.1039/c5sc02321a · Cited by 138 · see citing works
Glucocorticoids, genes and brain function
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Histone Lysine and Genomic Targets of Histone Acetyltransferases in Mammals
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Keeping it quiet: chromatin control of gammaherpesvirus latency
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Epigenetic control of gene regulation during development and disease: A view from the retina
Corso‐Díaz, X., Jaeger, C., Chaitankar, V., & Swaroop, A. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.03.002 · Cited by 129 · see citing works
“Due to their impact on chromatin structure and DNA accessibility, histones are key regulators of all major chromatin-related processes, including DNA transcription, replication and repair (Zentner and Henikoff, 2013).”
BackgroundHigh-resolution digital profiling of the epigenome
Zentner, G. E., & Henikoff, S. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3798 · Cited by 125 · see citing works
“…layer of regulatory information superimposed on the genome and includes nucleosome occupancy 1 , positioning 1 , composition 2 , modification 3 and dynamics 4 , as well as DNA methylation 5 ; it is shaped by the action of transcription factors (TFs) 6 , ATP-dependent chromatin remodellers 7…”
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“Epigenomic effects are assumed to be mediated primarily by chromatin modifying enzymes that act quickly (45).”
BackgroundBromodomains and Their Pharmacological Inhibitors
Gallenkamp, D., Gelato, K. A., Haendler, B., & Weinmann, H. (2014) · ChemMedChem · doi:10.1002/cmdc.201300434 · Cited by 126 · see citing works
ISWI chromatin remodeling complexes in the DNA damage response
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“This in turn may lead to the modulation of nucleosome dynamics by altering histone-DNA contacts or to the chromatin association of proteins that act on DNA or mediate signaling responses.(7) Many different types of histone modifications play essential roles in orchestrating DNA repair and DNA damage signaling, includi…”
BackgroundEmerging Roles for Polycomb-Group Proteins in Stem Cells and Cancer
Chan, H. L., & Morey, L. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.04.005 · Cited by 126 · see citing works
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Histone Tail Conformations: A Fuzzy Affair with DNA
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- Authors
- Zentner, G. E., & Henikoff, S.
- Affiliations
- Fred Hutch Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Henikoff, Steven
- Venue
- Nature Structural & Molecular Biology
- Published
- 2013-03
- Volume
- 20
- Issue
- 3
- Pages
- 259-266
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2034340491
- Cited by
- 923
- References
- 111
- Citations by year
- 2026: 22 · 2025: 33 · 2024: 57 · 2023: 39 · 2022: 45 · 2021: 60 · 2020: 63 · 2019: 82 · 2018: 75 · 2017: 84 · 2016: 76 · 2015: 106 · 2014: 125 · 2013: 52
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5u01hg004274-04)
- National Human Genome Research Institute (5U01 HG004274)
- National Cancer Institute (T32CA009657, U54CA143862)
- National Institute of Environmental Health Sciences (R01ES020116)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- nucleosome dynamics, histone modifications, chromatin, nucleosome mobility, nucleosome turnover, transcription, DNA replication, DNA repair
- MeSH terms
- Acetylation, Acylation, Adenosine Diphosphate, Chromatin, DNA, DNA Replication, Gene Expression Regulation, Glycosylation, Histones, Lysine, Methylation, Nucleosomes
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