CoChat
Sign Up
Cited by 62Genomics and Chromatin DynamicsEpigenetics and DNA MethylationNuclear Structure and Function

Semisynthesis of site-specifically succinylated histone reveals that succinylation regulates nucleosome unwrapping rate and DNA accessibility

Open access
Jing, Yihang, Ding, Dongbo, Tian, Gaofei, Kwan, Ka Chun Jonathan, Liu, Zheng, Ishibashi, Toyotaka, Li, Xiang David·2020·Nucleic Acids Research
DOI 10.1093/nar/gkaa663PMC PMC7515725
Open this paper in CoChat — free accountOpen PDF

Abstract

Posttranslational modifications (PTMs) of histones represent a crucial regulatory mechanism of nucleosome and chromatin dynamics in various of DNA-based cellular processes, such as replication, transcription and DNA damage repair. Lysine succinylation (Ksucc) is a newly identified histone PTM, but its regulation and function in chromatin remain poorly understood. Here, we utilized an expressed protein ligation (EPL) strategy to synthesize histone H4 with site-specific succinylation at K77 residue (H4K77succ), an evolutionarily conserved succinylation site at the nucleosomal DNA-histone interface. We then assembled mononucleosomes with the semisynthetic H4K77succ in vitro. We demonstrated that this succinylation impacts nucleosome dynamics and promotes DNA unwrapping from the histone surface, which allows proteins such as transcription factors to rapidly access buried regions of the nucleosomal DNA. In budding yeast, a lysine-to-glutamic acid mutation, which mimics Ksucc, at the H4K77 site reduced nucleosome stability and led to defects in DNA damage repair and telomere silencing in vivo. Our findings revealed this uncharacterized histone modification has important roles in nucleosome and chromatin dynamics.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/nar/gkaa663

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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 vast majority of studies to date, histone succinylation is associated with the opening of chromatin and increased gene transcription.

    “In the vast majority of these studies to date, histone succinylation is associated with the opening of chromatin and increased gene transcription.”

    From Loss of succinyl-CoA synthetase in mouse forebrain results in hypersuccinylation with perturbed neuronal transcription and metabolism (2023) · cites this paper as [46]

    The Introduction and Results and Discussion (page not supplied) report that H4K77 succinylation increases nucleosomal DNA accessibility; the succinylation-mimicking mutation also disrupts telomere silencing in yeast. The paper does not establish that the vast majority of studies find increased gene transcription, and its direct succinylation experiments do not measure transcription. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 44

  1. [1]Luger K., Mader A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997; 389: 251– 260. 9305837
  2. [2]McGinty R.K., Tan S. Nucleosome structure and function. Chem. Rev. 2015; 115: 2255– 2273. 25495456 PMC4378457
  3. [3]Polo S.E., Almouzni G. Chromatin dynamics after DNA damage: the legacy of the access-repair-restore model. DNA Repair (Amst). 2015; 36: 114– 121. 26429064 PMC5113751
  4. [5]Bowman G.D., Poirier M.G. Post-translational modifications of histones that influence nucleosome dynamics. Chem. Rev. 2015; 115: 2274– 2295. 25424540 PMC4375056
  5. [6]Huang H., Sabari B.R., Garcia B.A., Allis C.D., Zhao Y. SnapShot: histone modifications. Cell. 2014; 159: 458– 458. 25303536 PMC4324475
  6. [7]Ye J., Ai X., Eugeni E.E., Zhang L., Carpenter L.R., Jelinek M.A., Freitas M.A., Parthun M.R. Histone H4 lysine 91 acetylation a core domain modification associated with chromatin assembly. Mol. Cell. 2005; 18: 123– 130. 15808514 PMC2855496
  7. [8]Shimko J.C., North J.A., Bruns A.N., Poirier M.G., Ottesen J.J. Preparation of fully synthetic histone H3 reveals that acetyl-lysine 56 facilitates protein binding within nucleosomes. J. Mol. Biol. 2011; 408: 187– 204. 21310161 PMC3815667
  8. [9]Simon M., North J.A., Shimko J.C., Forties R.A., Ferdinand M.B., Manohar M., Zhang M., Fishel R., Ottesen J.J., Poirier M.G. Histone fold modifications control nucleosome unwrapping and disassembly. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 12711– 12716. 21768347 PMC3150920
  9. [10]Neumann H., Hancock S.M., Buning R., Routh A., Chapman L., Somers J., Owen-Hughes T., van Noort J., Rhodes D., Chin J.W. A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol. Cell. 2009; 36: 153– 163. 19818718 PMC2856916
  10. [13]Xie Z., Dai J., Dai L., Tan M., Cheng Z., Wu Y., Boeke J.D., Zhao Y. Lysine succinylation and lysine malonylation in histones. Mol. Cell. Proteomics. 2012; 11: 100– 107. 22389435 PMC3418837
  11. [14]Bao X., Xiong Y., Li X., Li X.D. A chemical reporter facilitates the detection and identification of lysine HMGylation on histones. Chem. Sci. 2018; 9: 7797– 7801. 30429988 PMC6194501
  12. [17]Kurmi K., Hitosugi S., Wiese E.K., Boakye-Agyeman F., Gonsalves W.I., Lou Z., Karnitz L.M., Goetz M.P., Hitosugi T. Carnitine palmitoyltransferase 1A has a lysine succinyltransferase activity. Cell Rep. 2018; 22: 1365– 1373. 29425493 PMC5826573
  13. [18]Li F., He X., Ye D., Lin Y., Yu H., Yao C., Huang L., Zhang J., Wang F., Xu S. et al. NADP(+)-IDH mutations promote hypersuccinylation that impairs mitochondria respiration and induces apoptosis resistance. Mol. Cell. 2015; 60: 661– 675. 26585387
  14. [19]Chen H., Xu H., Potash S., Starkov A., Belousov V.V., Bilan D.S., Denton T.T., Gibson G.E. Mild metabolic perturbations alter succinylation of mitochondrial proteins. J. Neurosci. Res. 2017; 95: 2244– 2252. 28631845 PMC5597472
  15. [20]Jing Y., Liu Z., Tian G., Bao X., Ishibashi T., Li X.D. Site-specific installation of succinyl lysine analog into histones reveals the effect of H2BK34 succinylation on nucleosome dynamics. Cell Chem Biol. 2018; 25: 166– 174. 29249693
  16. [21]Fenley A.T., Anandakrishnan R., Kidane Y.H., Onufriev A.V. Modulation of nucleosomal DNA accessibility via charge-altering post-translational modifications in histone core. Epigenet. Chromatin. 2018; 11: 11. PMC5856334 29548294
  17. [22]Muir T.W., Sondhi D., Cole P.A. Expressed protein ligation: a general method for protein engineering. Proc. Natl Acad. Sci. U.S.A. 1998; 95: 6705– 6710. 9618476 PMC22605
  18. [23]Luger K., Rechsteiner T.J., Richmond T.J. Expression and purification of recombinant histones and nucleosome reconstitution. Methods Mol. Biol. 1999; 119: 1– 16. 10804500
  19. [24]Little J.W., Kim B., Roland K.L., Smith M.H., Lin L.L., Slilaty S.N. Cleavage of LexA repressor. Methods Enzymol. 1994; 244: 266– 284. 7845214
  20. [25]Marty M.T., Baldwin A.J., Marklund E.G., Hochberg G.K., Benesch J.L., Robinson C.V. Bayesian deconvolution of mass and ion mobility spectra: from binary interactions to polydisperse ensembles. Anal. Chem. 2015; 87: 4370– 4376. 25799115 PMC4594776
  21. [26]Gansen A., Toth K., Schwarz N., Langowski J. Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure–a FRET study. Nucleic Acids Res. 2015; 43: 1433– 1443. 25589544 PMC4330349
  22. [27]Bohm V., Hieb A.R., Andrews A.J., Gansen A., Rocker A., Toth K., Luger K., Langowski J. Nucleosome accessibility governed by the dimer/tetramer interface. Nucleic Acids Res. 2011; 39: 3093– 3102. 21177647 PMC3082900
  23. [28]Luger K., Rechsteiner T.J., Flaus A.J., Waye M.M.Y., Richmond T.J. Characterization of nucleosome core particles containing histone proteins made in bacteria1. J. Mol. Biol. 1997; 272: 301– 311. 9325091
  24. [29]Li G., Widom J. Nucleosomes facilitate their own invasion. Nat. Struct. Mol. Biol. 2004; 11: 763– 769. 15258568
  25. [30]Clegg R.M. Fluorescence resonance energy transfer and nucleic acids. Methods Enzymol. 1992; 211: 353– 388. 1406315
  26. [31]Shukla M.S., Syed S.H., Montel F., Faivre-Moskalenko C., Bednar J., Travers A., Angelov D., Dimitrov S. Remosomes: RSC generated non-mobilized particles with approximately 180 bp DNA loosely associated with the histone octamer. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 1936– 1941. 20080697 PMC2836606
  27. [32]Wu C., Travers A. A ‘one-pot’assay for the accessibility of DNA in a nucleosome core particle. Nucleic Acids Res. 2004; 32: e122– e122. 15329384 PMC516079
  28. [33]Bustamante C., Chemla Y.R., Forde N.R., Izhaky D. Mechanical processes in biochemistry. Annu. Rev. Biochem. 2004; 73: 705– 748. 15189157
  29. [34]Liphardt J., Onoa B., Smith S.B., Tinoco I., Bustamante C. Reversible unfolding of single RNA molecules by mechanical force. Science. 2001; 292: 733– 737. 11326101
  30. [35]Li W., Chen P., Yu J., Dong L., Liang D., Feng J., Yan J., Wang P.Y., Li Q., Zhang Z. et al. FACT remodels the tetranucleosomal unit of chromatin fibers for gene transcription. Mol. Cell. 2016; 64: 120– 133. 27666592
  31. [36]Toulmay A., Schneiter R. A two-step method for the introduction of single or multiple defined point mutations into the genome of Saccharomyces cerevisiae. Yeast. 2006; 23: 825– 831. 16921548
  32. [37]Longtine M.S., McKenzie A., Demarini D.J., Shah N.G., Wach A., Brachat A., Philippsen P., Pringle J.R. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998; 14: 953– 961. 9717241
  33. [38]Xiao W. Yeast Protocols. 2006; Totowa, NJ Humana Press.
  34. [39]Lowary P.T., Widom J. New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol. 1998; 276: 19– 42. 9514715
  35. [40]Park Y.J., Dyer P.N., Tremethick D.J., Luger K. A new fluorescence resonance energy transfer approach demonstrates that the histone variant H2AZ stabilizes the histone octamer within the nucleosome. J. Biol. Chem. 2004; 279: 24274– 24282. 15020582
  36. [41]Gansen A., Valeri A., Hauger F., Felekyan S., Kalinin S., Toth K., Langowski J., Seidel C.A. Nucleosome disassembly intermediates characterized by single-molecule FRET. PNAS. 2009; 106: 15308– 15313. 19706432 PMC2741247
  37. [42]Fierz B., Kilic S., Hieb A.R., Luger K., Muir T.W. Stability of nucleosomes containing homogenously ubiquitylated H2A and H2B prepared using semisynthesis. J. Am. Chem. Soc. 2012; 134: 19548– 19551. 23163596 PMC3535264
  38. [43]Li G., Levitus M., Bustamante C., Widom J. Rapid spontaneous accessibility of nucleosomal DNA. Nat. Struct. Mol. Biol. 2005; 12: 46– 53. 15580276
  39. [44]Mihardja S., Spakowitz A.J., Zhang Y., Bustamante C. Effect of force on mononucleosomal dynamics. Proc. Natl Acad. Sci. U.S.A. 2006; 103: 15871– 15876. 17043216 PMC1635095
  40. [45]Bintu L., Ishibashi T., Dangkulwanich M., Wu Y.Y., Lubkowska L., Kashlev M., Bustamante C. Nucleosomal elements that control the topography of the barrier to transcription. Cell. 2012; 151: 738– 749. 23141536 PMC3508686
  41. [46]Hyland E.M., Cosgrove M.S., Molina H., Wang D., Pandey A., Cottee R.J., Boeke J.D. Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol. Cell. Biol. 2005; 25: 10060– 10070. 16260619 PMC1280264
  42. [47]Masumoto H., Hawke D., Kobayashi R., Verreault A. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature. 2005; 436: 294– 298. 16015338
  43. [48]Manohar M., Mooney A.M., North J.A., Nakkula R.J., Picking J.W., Edon A., Fishel R., Poirier M.G., Ottesen J.J. Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding. J. Biol. Chem. 2009; 284: 23312– 23321. 19520870 PMC2749105
  44. [49]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.D. Glutarylation of histone H4 Lysine 91 regulates chromatin dynamics. Mol. Cell. 2019; 76: 660– 675. 31542297

Cited by

Sorted by citations

Authors
Jing, Y., Ding, D., Tian, G., Kwan, K. C. J., Liu, Z., Ishibashi, T., & Li, X. D.
Affiliations
  • University of Hong Kong (HK)
  • Hong Kong University of Science and Technology (HK)
Corresponding author
  • Liu, Zheng
  • Ishibashi, Toyotaka
  • Li, Xiang David
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2020-08-07
Volume
48
Issue
17
Pages
9538-9549
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkaa663
PMC
PMC7515725
OpenAlex
W3048260234
Cited by
62
References
5
Citations by year
2026: 7 · 2025: 15 · 2024: 7 · 2023: 11 · 2022: 12 · 2021: 9 · 2020: 1
FWCI
2.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • National Natural Science Foundation of China (91753130, 21572191)
  • Hong Kong Research Grants Council (CRF C7029-15G, CRF C7028-19GF)
  • Areas of Excellence Scheme (AoE/P-705/16)
  • General Research Fund (17121120, 17126618, 17125917)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
expressed protein ligation, nucleosome unwrapping, DNA accessibility, nucleosome stability, chromatin dynamics, DNA repair, telomeric silencing, Saccharomyces cerevisiae
MeSH terms
LexA Repressor Protein, Bacterial Proteins, Chromatin, DNA, Histones, Lysine, Nucleosomes, Protein Processing, Post-Translational, Recombinant Proteins, Saccharomyces cerevisiae, Serine Endopeptidases, Xenopus Proteins, Fluorescence Resonance Energy Transfer

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