Lysine propionylation and butyrylation are novel post-translational modifications in histones
Open accessAbstract
The positively charged lysine residue plays an important role in protein folding and functions. Neutralization of the charge often has a profound impact on the substrate proteins. Accordingly all the known post-translational modifications at lysine have pivotal roles in cell physiology and pathology. Here we report the discovery of two novel, in vivo lysine modifications in histones, lysine propionylation and butyrylation. We confirmed, by in vitro labeling and peptide mapping by mass spectrometry, that two previously known acetyltransferases, p300 and CREB-binding protein, could catalyze lysine propionylation and lysine butyrylation in histones. Finally p300 and CREB-binding protein could carry out autopropionylation and autobutyrylation in vitro. Taken together, our results conclusively establish that lysine propionylation and lysine butyrylation are novel post-translational modifications. Given the unique roles of propionyl-CoA and butyryl-CoA in energy metabolism and the significant structural changes induced by the modifications, the two modifications are likely to have important but distinct functions in the regulation of biological processes.
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.
Integrity signals
Registry
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.
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?
Large variety of novel histone marks, such as formylation, propionylation, butyrylation, malonylation, and succinylation, have been identified by tandem mass spectrometry.
“In fact, a large variety of novel histone marks, such as formylation, propionylation, butyrylation, malonylation and succinylation have recently been identified by tandem mass spectrometry (Chen et al., 2007; Wisniewski et al., 2008; Xie et al., 2012).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Chen et al., 2007
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
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
(1978) · Biochemical Education · doi:10.1016/0307-4412(78)90049-3 · Cited by 5,073 · see citing works
ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS
Allfrey, V. G., Faulkner, R. D., & Mirsky, A. E. (1964) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.51.5.786 · Cited by 2,649 · see citing works
Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Gu, W., & Roeder, R. G. (1997) · Cell · doi:10.1016/s0092-8674(00)80521-8 · Cited by 2,559 · see citing works
Self-citationDent, S., Denu, J. M., & Allis, C. D. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.81 · Cited by 1,844 · see citing works
Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications
Walsh, C. T., Garneau‐Tsodikova, S., & Gatto, G. J. J. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200501023 · Cited by 1,609 · see citing works
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,496 · see citing works
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487 · see citing works
Self-citationHistones and histone modifications
Peterson, C. L., & Laniel, M.-A. (2004) · Current Biology · doi:10.1016/j.cub.2004.07.007 · Cited by 1,313 · see citing works
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295 · see citing works
Histone and chromatin cross-talk
Fischle, W., Wang, Y., & Allis, C. D. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00013-9 · Cited by 1,207 · see citing works
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204 · see citing works
Acetylation: a regulatory modification to rival phosphorylation?
Kouzarides, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.6.1176 · Cited by 1,155 · see citing works
Sauve, A. A., Wolberger, C., Schramm, V. L., & Boeke, J. D. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133500 · Cited by 763 · see citing works
Tip60-Dependent Acetylation of p53 Modulates the Decision between Cell-Cycle Arrest and Apoptosis
Tang, Y., Luo, J., Zhang, W., & Gu, W. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.021 · Cited by 724 · see citing works
Self-citationRecruitment of p300/CBP in p53-Dependent Signal Pathways
Avantaggiati, M. L., Ogryzko, V. V., Gardner, K., Giordano, A., Levine, A. S., & Kelly, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80304-9 · Cited by 668 · see citing works
Deciphering the Transcriptional Histone Acetylation Code for a Human Gene
Agalioti, T., Chen, G., & Thanos, D. (2002) · Cell · doi:10.1016/s0092-8674(02)01077-2 · Cited by 639 · see citing works
Synergistic activation of transcription by CBP and p53
Gu, W., Shi, X.-L., & Roeder, R. G. (1997) · Nature · doi:10.1038/42972 · Cited by 596 · see citing works
Self-citationThe diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases
Yang, X. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh252 · Cited by 513 · see citing works
Posttranslational Modification of Proteins: Expanding Nature's Inventory
Walsh, C. T. (2005) · Cited by 484 · see citing works
Linking the epigenetic ‘language’ of covalent histone modifications to cancer
Hake, S. B., Xiao, A., & Allis, C. D. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601575 · Cited by 384 · see citing works
Organismal Differences in Post-translational Modifications in Histones H3 and H4
Garcia, B. A., Hake, S. B., Diaz, R. L., Kauer, M., Morris, S. A., Recht, J., Shabanowitz, J., Mishra, N., Strahl, B. D., Allis, C. D., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607900200 · Cited by 314 · see citing works
Proteomic Analysis of Integral Plasma Membrane Proteins
Zhao, Y., Zhang, W., Kho, Y., & Zhao, Y. (2004) · Analytical Chemistry · doi:10.1021/ac0354037 · Cited by 237 · see citing works
Self-citationChen, Y., Kwon, S. W., Kim, S. C., & Zhao, Y. (2005) · Journal of Proteome Research · doi:10.1021/pr049754t · Cited by 177 · see citing works
Self-citationPrecise Characterization of Human Histones in the H2A Gene Family by Top Down Mass Spectrometry
Boyne, M. T., Pesavento, J. J., Mizzen, C. A., & Kelleher, N. L. (2006) · Journal of Proteome Research · doi:10.1021/pr050269n · Cited by 157 · see citing works
Cardiac histone acetylation – therapeutic opportunities abound
McKinsey, T. A., & Olson, E. N. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.02.002 · Cited by 131 · see citing works
Medzihradszky, K. F., Zhang, X., Chalkley, R. J., Guan, S., McFarland, M. A., Chalmers, M. J., Marshall, A. G., Diaz, R., Allis, C. D., & Burlingame, A. L. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400041-mcp200 · Cited by 94 · see citing works
The Characterization of Protein Post-Translational Modifications by Mass Spectrometry
Schweppe, R. E., Haydon, C. E., Lewis, T. S., Resing, K. A., & Ahn, N. G. (2003) · Accounts of Chemical Research · doi:10.1021/ar020143l · Cited by 93 · see citing works
King, M., & Reiss, P. D. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90412-9 · Cited by 90 · see citing works
Histone H4 lysine 16 acetylation breaks the genome's silence.
Shia, W.-J., Pattenden, S. G., & Workman, J. L. (2006) · Genome biology · doi:10.1186/gb-2006-7-5-217 · Cited by 61 · see citing works
Dutnall, R. N., Tafrov, S. T., Sternglanz, R., & Ramakrishnan, V. (1998) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1998.63.501 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
Tan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.008 · Cited by 1,902 · see citing works
Self-citationThe growing landscape of lysine acetylation links metabolism and cell signalling
Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E., & Mann, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3841 · Cited by 1,324 · see citing works
Identification of lysine succinylation as a new post-translational modification
Zhang, Z., Tan, M., Xie, Z., Dai, L., Chen, Y., & Zhao, Y. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.495 · Cited by 1,027 · see citing works
Self-citationSIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.001 · Cited by 1,000 · see citing works
Self-citationLysine glutarylation is a protein posttranslational modification regulated by SIRT5
Tan, M., Peng, C., Anderson, K. A., Chhoy, P., Xie, Z., Dai, L., Park, J., Chen, Y., Huang, H., Zhang, Y., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.014 · Cited by 844 · see citing works
Self-citationIntracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation
Sabari, B. R., Tang, Z., Huang, H., Yong-Gonzalez, V., Molina, H., Kong, H. E., Dai, L., Shimada, M., Cross, J. R., Zhao, Y., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.029 · Cited by 659 · see citing works
Self-citationFeldman, J. L., Baeza, J., & Denu, J. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.511261 · Cited by 637 · see citing works
Fellows, R., Denizot, J., Stellato, C., Cuomo, A., Jain, P., Stoyanova, E., Balázsi, S., Hajnády, Z., Liebert, A., Kazakevych, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02651-5 · Cited by 568 · see citing works
Nishida, Y., Rardin, M. J., Carrico, C., He, W., Sahu, A. K., Gut, P., Najjar, R., Fitch, M., Hellerstein, M., Gibson, B. W., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.022 · Cited by 481 · see citing works
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442 · see citing works
SnapShot: histone modifications
Huang, H., Sabari, B. R., Garcia, B. A., Allis, C. D., & Zhao, Y. (2014) · Cell · doi:10.1016/j.cell.2014.09.037 · Cited by 439 · see citing works
Self-citationChemical mechanisms of histone lysine and arginine modifications
Smith, B. C., & Denu, J. M. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2008.06.005 · Cited by 390 · see citing works
Mitochondrial sirtuins: regulators of protein acylation and metabolism
He, W., Newman, J. C., Wang, M. Z., Ho, L., & Verdin, E. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.07.004 · Cited by 262 · see citing works
Compartmentalised acyl-CoA metabolism and roles in chromatin regulation
Trefely, S., Lovell, C. D., Snyder, N. W., & Wellen, K. E. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.005 · Cited by 272 · see citing works
Sirtuin catalysis and regulation
Feldman, J. L., Dittenhafer-Reed, K. E., & Denu, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.378877 · Cited by 248 · see citing works
Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism
Miro-Blanch, J., & Yanes, O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00638 · Cited by 195 · see citing works
Kelly, R. D. W., Chandru, A., Watson, P. J., Song, Y., Blades, M., Robertson, N. S., Jamieson, A. G., Schwabe, J. W. R., & Cowley, S. M. (2018) · Scientific Reports · doi:10.1038/s41598-018-32927-9 · Cited by 138 · see citing works
He, D., Wang, Q., Li, M., Damaris, R. N., Yi, X., Cheng, Z., & Yang, P. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00805 · Cited by 124 · see citing works
Montellier, E., Rousseaux, S., Zhao, Y., & Khochbin, S. (2012) · BioEssays · doi:10.1002/bies.201100141 · Cited by 116 · see citing works
Self-citationLiu, Y., Li, M., Fan, M., Song, Y., Yu, H., Zhi, X., Xiao, K., Lai, S., Zhang, J., Jin, X., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.11.025 · Cited by 106 · see citing works
Yao, Y., Bade, R., Li, G., Zhang, A., Zhao, H., Fan, L., Zhu, R., & Yuan, J. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01277-6 · Cited by 86 · see citing works
Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism
Pougovkina, O., te Brinke, H., Wanders, R. J. A., Houten, S. M., & de Boer, V. C. J. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9684-9 · Cited by 80 · see citing works
Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., Zhang, J., et al. (2019) · PLOS ONE · doi:10.1371/journal.pone.0211796 · Cited by 72 · see citing works
Self-citationHøgh, R. I., Møller, S. H., Jepsen, S. D., Mellergaard, M., Lund, A., Pejtersen, M., Fitzner, E., Andresen, L., & Skov, S. (2020) · The FASEB Journal · doi:10.1096/fj.202000162r · Cited by 56 · see citing works
Sirtuin activation as a therapeutic approach against inborn errors of metabolism
Bleeker, J. C., & Houtkooper, R. H. (2016) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-016-9939-8 · Cited by 11 · see citing works
- Authors
- Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S. C., Falck, J. R., Peng, J., Gu, W., & Zhao, Y.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Columbia University (US)
- Emory University (US)
- Corresponding author
- Zhao, Yingming
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 6
- Issue
- 5
- Pages
- 812-819
- ISSN
- 1535-9476 (ISSN-L)
- PMC
- PMC2911958
- OpenAlex
- W2117514345
- Cited by
- 764
- References
- 31
- Citations by year
- 2026: 47 · 2025: 48 · 2024: 49 · 2023: 57 · 2022: 59 · 2021: 59 · 2020: 51 · 2019: 55 · 2018: 46 · 2017: 44 · 2016: 53 · 2015: 48 · 2014: 32 · 2013: 25 · 2012: 23
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular & Cellular Proteomics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 025688, P50AG025688)
- National Cancer Institute (R01CA126832, R33CA107943, CA 107943, CA104843, CA098821, R01CA104843, R01CA098821, R21CA107943)
- National Institute of General Medical Sciences (GM-31278, R01GM031278)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- histone modifications, P300, CREB-binding protein, histone acetyltransferase, propionyl-CoA, butyryl-CoA
- MeSH terms
- Acyl Coenzyme A, Amino Acid Sequence, Chromatography, High Pressure Liquid, Histones, Humans, Lysine, Molecular Sequence Data, Peptides, Protein Processing, Post-Translational, Tumor Suppressor Protein p53, Proteomics, p300-CBP Transcription Factors, Tandem Mass Spectrometry
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
