Evidence map›Paper›PMID 33313896›Full record

ArticleNucleic acids research2021

Identification of lysine isobutyrylation as a new histone modification mark.

Zhesi Zhu, Zhen Han, Levon Halabelian, Xiangkun Yang, Jun Ding, Nawei Zhang, Liza Ngo, Jiabao Song, Hong Zeng, Maomao He and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
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  4. Article
  5. Article
  6. Article
  7. Article
  8. The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026
    Review
  9. Review
  10. Biochemistry and regulation of histone lysine L-lactylation.Nature reviews. Molecular cell biology · 2026
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026
    Review
  16. Review
  17. Article
  18. Discovery and Profiling of Protein CysteineMolecules (Basel, Switzerland) · 2025
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Zhesi ZhuDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Zhen HanDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Levon HalabelianStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Xiangkun YangDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Jun DingBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Nawei ZhangChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Liza NgoDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Jiabao SongDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Hong ZengStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Maomao HeDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Yingming ZhaoBen May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Cheryl H ArrowsmithStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Minkui LuoChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Michael G BartlettDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Y George ZhengDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
University of Georgia · USMemorial Sloan Kettering Cancer Center · USUniversity of Chicago · USUniversity of Toronto · CAUniversity Health Network · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI LIU, CAMBRIAN YANGSHAO · 1990 to 2025
$29.8M
Interrogating Protein Methyltransferases with Integrated ApproachesR35GM131858 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Minkui Luo · 2019 to 2026
$6.3M
Biochemistry of the lysine beta-hydroxybutyrylation pathwayR01DK118266 · NIDDK · UNIVERSITY OF CHICAGO · PI COLE, PHILIP A, ZHAO, YINGMING · 2018 to 2021
$2.1M
Probing short and long term consequences of Small and Large Bowel Microbiota Transplants on Host Physiology: Implications for the development of future live biotherapeuticsR01DK138072 · NIDDK · UNIVERSITY OF CHICAGO · PI EUGENE B CHANG, Kristina Brooke Martinez-Guryn · 2024 to 2026
$2.1M
Systems-wide analysis of histone lysine 2-hydroxyisobutyrylation pathwayR01GM115961 · NIGMS · UNIVERSITY OF CHICAGO · PI ZHAO, YINGMING · 2016 to 2019
$1.8M
National Science Foundation 1507741National Science Foundation 1808087NCI NIH HHS P30 CA008748NIDDK NIH HHS P30 DK042086NIDDK NIH HHS R01 DK118266NIDDK NIH HHS R01 DK138072NIGMS NIH HHS R01 GM115961NIGMS NIH HHS R35 GM131858Wellcome Trust
6 · The paper itself

Abstract

Short-chain acylations of lysine residues in eukaryotic proteins are recognized as essential posttranslational chemical modifications (PTMs) that regulate cellular processes from transcription, cell cycle, metabolism, to signal transduction. Lysine butyrylation was initially discovered as a normal straight chain butyrylation (Knbu). Here we report its structural isomer, branched chain butyrylation, i.e. lysine isobutyrylation (Kibu), existing as a new PTM on nuclear histones. Uniquely, isobutyryl-CoA is derived from valine catabolism and branched chain fatty acid oxidation which is distinct from the metabolism of n-butyryl-CoA. Several histone acetyltransferases were found to possess lysine isobutyryltransferase activity in vitro, especially p300 and HAT1. Transfection and western blot experiments showed that p300 regulated histone isobutyrylation levels in the cell. We resolved the X-ray crystal structures of HAT1 in complex with isobutyryl-CoA that gleaned an atomic level insight into HAT-catalyzed isobutyrylation. RNA-Seq profiling revealed that isobutyrate greatly affected the expression of genes associated with many pivotal biological pathways. Together, our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology.

Indexed as

Histone CodeProtein Processing, Post-TranslationalAcylationAcyl Coenzyme AAmino Acid SequenceChromatography, High Pressure LiquidCrystallography, X-RayHEK293 CellsHistone AcetyltransferasesHistonesHumansIsobutyratesLysine AcetyltransferasesModels, Molecularp300-CBP-Associated Factorp300-CBP Transcription FactorsAcyl Coenzyme AHistone Acetyltransferaseshistone acetyltransferase type B complexHistonesIsobutyratesisobutyric acidisobutyryl-coenzyme ALysine Acetyltransferasesp300-CBP-Associated Factorp300-CBP Transcription FactorsRecombinant ProteinsValine

Identifiers

PMID33313896
PMCPMC7797053
OpenAlexW3115758135

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.