CoChat
Sign Up
Cited by 87Genomics and Chromatin DynamicsEpigenetics and DNA MethylationCancer-related gene regulation

Histone succinylation and its function on the nucleosome

Open access
Liu, Jiayi, Shangguan, Yu, Tang, Donge, Dai, Yong·2021·Journal of Cellular and Molecular Medicine
DOI 10.1111/jcmm.16676PMC PMC8335665
Open this paper in CoChat — free accountOpen PDF

Abstract

Protein post‐translational modifications (PTMs) of histones are ubiquitous regulatory mechanisms involved in many biological processes, including replication, transcription, DNA damage repair and ontogenesis. Recently, many short‐chain acylation histone modifications have been identified by mass spectrometry (MS). Lysine succinylation (Ksuc or Ksucc) is a newly identified histone PTM that changes the chemical environment of histones and is similar to other acylation modifications; lysine succinylation appears to accumulate at transcriptional start sites and to correlate with gene expression. Although numerous studies are ongoing, there is a lack of reviews on the Ksuc of histones. Here, we review lysine succinylation sites on histones, including the chemical characteristics and the mechanism by which lysine succinylation influences nucleosomal structure, chromatin dynamics and several diseases and then discuss lysine succinylation regulation to identify theoretical and experimental proof of Ksuc on histones and in diseases to inspire further research into histone lysine succinylation as a target of disease treatment in the future.

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 · 10.1111/jcmm.16676

Cites

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 [27]

    The section on changes in nucleosome structure (page unavailable) says histone succinylation weakens DNA–histone binding and can contribute to transcription; it also reports a correlation between promoter succinylation and transcriptional activity. But it limits the mechanistic evidence to in vitro experiments and does not establish that the vast majority of studies find both chromatin opening and increased transcription. (LLM, conf=0.84)

    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.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 71 · Cited by 87

Research works printed but not linked: 57

  1. [1]Ruthenburg AJ, Li H, Patel DJ, Allis CD. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007; 8(12): 983‐ 994. 10.1038/nrm2298 18037899 PMC4690530 · DOI
  2. [2]Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014; 15(11): 703‐ 708. 10.1038/nrm3890 25315270 · DOI · Paper page
  3. [4]Li X, Egervari G, Wang Y, Berger SL, Lu Z. Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat Rev Mol Cell Biol. 2018; 19(9): 563‐ 578. 10.1038/s41580-018-0029-7 29930302 PMC6907087 · DOI
  4. [5]Xie Z, Dai J, Dai L, et al. Lysine succinylation and lysine malonylation in histones. Mol Cell Proteomics. 2012; 11(5): 100‐ 107. 10.1074/mcp.M111.015875 22389435 PMC3418837 · DOI · Paper page
  5. [6]Weinert BT, Scholz C, Wagner SA, et al. Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep. 2013; 4(4): 842‐ 851. 10.1016/j.celrep.2013.07.024 23954790 · DOI
  6. [9]Kawai Y, Fujii H, Okada M, Tsuchie Y, Uchida K, Osawa T. Formation of Nε‐(succinyl)lysine in vivo: a novel marker for docosahexaenoic acid‐derived protein modification. J Lipid Res. 2006; 47(7): 1386‐ 1398. 10.1194/jlr.M600091-JLR200 16582421 · DOI · Paper page
  7. [12]Rardin MJ, He W, Nishida Y, et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 2013; 18(6): 920‐ 933. 10.1016/j.cmet.2013.11.013 24315375 PMC4105152 · DOI
  8. [14]Sadhukhan S, Liu X, Ryu D, et al. Metabolomics‐assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Proc Natl Acad Sci U S A. 2016; 113(16): 4320‐ 4325. 10.1073/pnas.1519858113 27051063 PMC4843474 · DOI
  9. [15]Wang G, Meyer JG, Cai W, et al. Regulation of UCP1 and mitochondrial metabolism in brown adipose tissue by reversible succinylation. Mol Cell. 2019; 74(4): 844– 857.e7. 10.1016/j.molcel.2019.03.021 31000437 PMC6525068 · DOI
  10. [16]Sabari BR, Zhang D, Allis CD, Zhao Y. Metabolic regulation of gene expression through histone acylations. Nat Rev Mol Cell Biol. 2017; 18(2): 90‐ 101. 10.1038/nrm.2016.140 27924077 PMC5320945 · DOI
  11. [17]Barnes CE, English DM, Cowley SM. Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription. Essays Biochem. 2019; 63(1): 97‐ 107. 10.1042/EBC20180061 30940741 PMC6484784 · DOI
  12. [18]Ye J, Ai X, Eugeni EE, et al. Histone H4 lysine 91 acetylation a core domain modification associated with chromatin assembly. Mol Cell. 2005; 18(1): 123‐ 130. 10.1016/j.molcel.2005.02.031 15808514 PMC2855496 · DOI
  13. [19]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(7048): 294‐ 298. 10.1038/nature03714 16015338 · DOI
  14. [20]Simon M, North JA, Shimko JC, et al. Histone fold modifications control nucleosome unwrapping and disassembly. PNAS. 2011; 108(31): 12711‐ 12716. 10.1073/pnas.1106264108 21768347 PMC3150920 · DOI
  15. [21]Neumann H, Hancock SM, Buning R, et al. A method for genetically installing site‐specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell. 2009; 36(1): 153‐ 163. 10.1016/j.molcel.2009.07.027 19818718 PMC2856916 · DOI
  16. [22]Hirschey MD, Zhao Y. Metabolic regulation by lysine malonylation, succinylation, and glutarylation. Mol Cell Proteomics. 2015; 14(9): 2308‐ 2315. 10.1074/mcp.R114.046664 25717114 PMC4563717 · DOI
  17. [23]Dai J, Hyland EM, Yuan DS, Huang H, Bader JS, Boeke JD. Probing nucleosome function: a highly versatile library of synthetic histone H3 and H4 mutants. Cell. 2008; 134(6): 1066‐ 1078. 10.1016/j.cell.2008.07.019 18805098 PMC2701395 · DOI
  18. [24]Jing Y, Ding D, Tian G, et al. Semisynthesis of site‐specifically succinylated histone reveals that succinylation regulates nucleosome unwrapping rate and DNA accessibility. Nucleic Acids Res. 2020; 48(17): 9538‐ 9549. 10.1093/nar/gkaa663 32766790 PMC7515725 · DOI · Paper page
  19. [25]Jing Y, Liu Z, Tian G, Bao X, Ishibashi T, Li XD. Site‐specific installation of succinyl lysine analog into histones reveals the effect of H2BK34 succinylation on nucleosome dynamics. Cell Chem Biol. 2018; 25(2): 166‐ 174.e7. 10.1016/j.chembiol.2017.11.005 29249693 · DOI
  20. [26]Hyland EM, Cosgrove MS, Molina H, et al. Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol Cell Biol. 2005; 25(22): 10060‐ 10070. 10.1128/MCB.25.22.10060-10070.2005 16260619 PMC1280264 · DOI
  21. [27]Smestad J, Erber L, Chen Y, Maher III LJ. Chromatin succinylation correlates with active gene expression and is perturbed by defective TCA Cycle Metabolism. iScience. 2018; 2: 63‐ 75. 10.1016/j.isci.2018.03.012 29888767 PMC5993049 · DOI
  22. [29]Simithy J, Sidoli S, Yuan ZF, et al. Characterization of histone acylations links chromatin modifications with metabolism. Nat Commun. 2017; 8(1): 1141. 10.1038/s41467-017-01384-9 29070843 PMC5656686 · DOI
  23. [30]Wellen KE, Thompson CB. A two‐way street: reciprocal regulation of metabolism and signalling. Nat Rev Mol Cell Biol. 2012; 13(4): 270‐ 276. 10.1038/nrm3305 22395772 · DOI · Paper page
  24. [32]Trefely S, Lovell CD, Snyder NW, Wellen KE. Compartmentalised acyl‐CoA metabolism and roles in chromatin regulation. Mol Metab. 2020; 38: 100941. 10.1016/j.molmet.2020.01.005 32199817 PMC7300382 · DOI · Paper page
  25. [33]Philip LP, Leonard CM, Samuel BH. Nuclear envelope permeability. Nature. 1975; 254: 109‐ 114. 1117994
  26. [35]Palmieri F. The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch. 2004; 447(5): 689‐ 709. 10.1007/s00424-003-1099-7 14598172 · DOI
  27. [36]Monné M, Miniero DV, Iacobazzi V, Bisaccia F, Fiermonte G. The mitochondrial oxoglutarate carrier: from identification to mechanism. J Bioenerg Biomembr. 2013; 45(1‐2): 1‐ 13. 10.1007/s10863-012-9475-7 23054077 · DOI
  28. [38]Rizzo C, Boenzi S, Inglese R, et al. Measurement of succinyl‐carnitine and methylmalonyl‐carnitine on dried blood spot by liquid chromatography‐tandem mass spectrometry. Clin Chim Acta. 2014; 429: 30‐ 33. 10.1016/j.cca.2013.11.016 24269713 · DOI
  29. [39]Violante S, Ijlst L, Ruiter J, et al. Substrate specificity of human carnitine acetyltransferase: Implications for fatty acid and branched‐chain amino acid metabolism. Biochim Biophys Acta. 2013; 1832(6): 773‐ 779. 10.1016/j.bbadis.2013.02.012 23485643 · DOI
  30. [40]Kurmi K, Hitosugi S, Wiese EK, et al. Carnitine palmitoyltransferase 1A has a lysine succinyltransferase activity. Cell Rep. 2018; 22(6): 1365‐ 1373. 10.1016/j.celrep.2018.01.030 29425493 PMC5826573 · DOI
  31. [41]Li F, He X, Ye D, et al. NADP(+)‐IDH mutations promote hypersuccinylation that impairs mitochondria respiration and induces apoptosis resistance. Mol Cell. 2015; 60(4): 661‐ 675. 10.1016/j.molcel.2015.10.017 26585387 · DOI · Paper page
  32. [42]Palmieri F, Stipani I, Quagliariello E, Klingenberg M. Kinetic study of the tricarboxylate carrier in rat liver mitochondria. Eur J Biochem. 1972; 26(4): 587‐ 594. 10.1111/j.1432-1033.1972.tb01801.x 5025933 · DOI
  33. [43]Fiermonte G, Palmieri L, Dolce V, Lasorsa FM, Palmieri F, Runswick MJ, Walker JE. The Sequence, Bacterial Expression, and Functional Reconstitution of the Rat Mitochondrial Dicarboxylate Transporter Cloned via Distant Homologs in Yeast and Caenorhabditis elegans. J Biol Chem. 1998; 273(38): 24754– 24759. 10.1074/jbc.273.38.24754 9733776 · DOI
  34. [44]Hausinger RP. FeII/α‐ketoglutarate‐dependent hydroxylases and related enzymes. Crit Rev Biochem Mol Biol. 2004; 39(1): 21‐ 68. 10.1080/10409230490440541 15121720 · DOI · Paper page
  35. [45]Westin MA, Hunt MC, Alexson SE. The identification of a succinyl‐CoA thioesterase suggests a novel pathway for succinate production in peroxisomes. J Biol Chem. 2005; 280(46): 38125‐ 38132. 10.1074/jbc.M508479200 16141203 · DOI
  36. [46]Ellis JM, Bowman CE, Wolfgang MJ. Metabolic and tissue‐specific regulation of acyl‐CoA metabolism. PLoS One. 2015; 10(3): e0116587. 10.1371/journal.pone.0116587 25760036 PMC4356623 · DOI
  37. [47]Antonenkov VD, Hiltunen JK. Transfer of metabolites across the peroxisomal membrane. Biochim Biophys Acta. 2012; 1822(9): 1374‐ 1386. 10.1016/j.bbadis.2011.12.011 22206997 · DOI
  38. [48]Yokoyama A, Katsura S, Sugawara A. Biochemical analysis of histone succinylation. Biochem Res Int. 2017; 2017: 8529404. 10.1155/2017/8529404 29225971 PMC5684591 · DOI
  39. [49]Yang G, Yuan Y, Yuan H, et al. Histone acetyltransferase 1 is a succinyltransferase for histones and non‐histones and promotes tumorigenesis. EMBO Rep. 2021; 22(2): e50967. 10.15252/embr.20205096726 33372411 PMC7857430 · DOI
  40. [50]Kaczmarska Z, Ortega E, Goudarzi A, et al. Structure of p300 in complex with acyl‐CoA variants. Nat Chem Biol. 2017; 13(1): 21‐ 29. 10.1038/nchembio.2217 27820805 PMC5757799 · DOI
  41. [51]Ringel AE, Wolberger C. Structural basis for acyl‐group discrimination by human Gcn5L2. Acta Crystallogr D Struct Biol. 2016; 72(7): 841‐ 848. 10.1107/S2059798316007907 27377381 PMC4932917 · DOI
  42. [52]Wang Y, Jin J, Chung MWH, Feng L, Sun H, Hao Q. Identification of the YEATS domain of GAS41 as a pH‐dependent reader of histone succinylation. PNAS. 2018; 115(10): 2365‐ 2370. 10.1073/pnas.1717664115 29463709 PMC5877980 · DOI
  43. [53]Brownell JE, Zhou J, Ranalli T, et al. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996; 84(6): 843‐ 851. 10.1016/s0092-8674(00)81063-6 8601308 · DOI
  44. [54]Wang L, Dent SY. Functions of SAGA in development and disease. Epigenomics. 2014; 6(3): 329‐ 339. 10.2217/epi.14.22 25111486 PMC4159956 · DOI
  45. [55]Tong Y, Guo D, Yan D, et al. KAT2A succinyltransferase activity‐mediated 14–3‐3ζ upregulation promotes β‐catenin stabilization‐dependent glycolysis and proliferation of pancreatic carcinoma cells. Cancer Lett. 2020; 469: 1‐ 10. 10.1016/j.canlet.2019.09.015 31610265 · DOI
  46. [56]Tian Q, Feetham MC, Tao WA, He XC, Li L, Aebersold R, Hood L. Proteomic analysis identifies that 14‐3‐3ζ interacts with β‐catenin and facilitates its activation by Akt. PNAS. 2004; 101(43): 15370‐ 15375. 10.1073/pnas.0406499101 15492215 PMC524456 · DOI
  47. [57]Chen CH, Chuang SM, Yang MF, Liao JW, Yu SL, Chen JJ. A novel function of YWHAZ/β‐catenin axis in promoting epithelial‐mesenchymal transition and lung cancer metastasis. Mol Cancer Res. 2012; 10(10): 1319‐ 1331. 10.1158/1541-7786.MCR-12-0189 22912335 · DOI
  48. [58]Yuan Y, Yuan H, Yang G, et al. IFN‐α confers epigenetic regulation of HBV cccDNA minichromosome by modulating GCN5‐mediated succinylation of histone H3K79 to clear HBV cccDNA. Clin Epigenetics. 2020; 12(1): 135. 10.1186/s13148-020-00928-z 32894195 PMC7487718 · DOI
  49. [59]Sun TT, He J, Liang Q, et al. LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov. 2016; 6(7): 784‐ 801. 10.1158/2159-8290.CD-15-0921 27147598 · DOI
  50. [61]Guo Z, Pan F, Peng L, et al. Systematic proteome and lysine succinylome analysis reveals the enhanced cell migration by hyposuccinylation in esophageal squamous cell cancer. Mol Cell Proteomics. 2021; 20: 100053. 10.1074/mcp.RA120.002150 PMC7970140 33561546 · DOI
  51. [63]Hang T, Chen W, Wu M, et al. Structural insights into the molecular mechanism underlying SIRT5‐catalyzed desuccinylation of histone peptides. Biochem J. 2019; 476(2): 211‐ 223. 10.1042/BCJ20180745 30523058 · DOI
  52. [64]Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 2006; 20(9): 1075‐ 1080. 10.1101/gad.1399706 16618798 PMC1472467 · DOI · Paper page
  53. [65]Barber MF, Michishita‐Kioi E, Xi Y, et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012; 487(7405): 114‐ 118. 10.1038/nature11043 22722849 PMC3412143 · DOI
  54. [66]Li L, Shi L, Yang S, et al. SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability. Nat Commun. 2016; 7: 12235. 10.1038/ncomms12235 27436229 PMC4961794 · DOI
  55. [67]Houtkooper RH, Canto C, Wanders RJ, Auwerx J. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev. 2010; 31(2): 194‐ 223. 10.1210/er.2009-0026 20007326 PMC2852209 · DOI · Paper page
  56. [68]Huang H, Sabari BR, Garcia BA, Allis CD, Zhao Y. SnapShot: histone modifications. Cell. 2014; 159(2): pp. 458–458. e1. 10.1016/j.cell.2014.09.037 PMC4324475 25303536 · DOI · Paper page
  57. [69]Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019; 574(7779): 575‐ 580. 10.1038/s41586-019-1678-1 31645732 PMC6818755 · DOI · Paper page

Authors
Liu, J., Shangguan, Y., Tang, D., & Dai, Y.
Affiliations
Southern University of Science and Technology (CN)
Corresponding author
  • Tang, Donge
  • Dai, Yong
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2021-06-23
Volume
25
Issue
15
Pages
7101-7109
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/jcmm.16676
PMC
PMC8335665
OpenAlex
W3173450631
Cited by
87
References
71
Citations by year
2026: 16 · 2025: 22 · 2024: 12 · 2023: 24 · 2022: 12 · 2021: 1
FWCI
1.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Science and Technology Planning Project of Guangdong Province (2017B020209001)
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 › Cancer-related gene regulation
Keywords
histone modifications, nucleosome structure, chromatin dynamics, transcription start sites, gene expression regulation, disease targets
MeSH terms
Animals, Humans, Nucleosomes, Succinates, Histone Code

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