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Crotonylation: A novel layer of the epigenetic landscape in disease

Yifei Ma1, Yujie Zhang2, Lianjing Cao3

  • 1Pancreatic Disease Institute, Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, the Affiliated Hospital of Qingdao University, Qingdao University, Shandong, 266000, China; College of Public Health, Qingdao University, Shandong, 266071, China.

Cancer Letters
|May 15, 2026
PubMed

Insights

Crotonylation, a metabolic sensor, regulates gene expression and cellular processes. Targeting this epigenetic modification offers potential for cancer therapy and diagnostics.

Area of Science:

  • Biochemistry
  • Epigenetics
  • Metabolomics

Background:

  • Crotonylation is a lysine acylation linking metabolism and epigenetics.
  • The crotonyl group is recognized by specific
  • readers
  • (e.g., YEATS/DPF), influencing protein conformation.
  • Crotonyl-CoA, derived from various metabolic pathways, acts as a direct sensor for crotonylation levels.

Purpose of the Study:

  • To review the multifaceted roles of crotonylation in cellular functions.
  • To highlight crotonylation's involvement in cancer progression and therapeutic potential.
  • To discuss recent technological advancements in studying crotonylation.

Main Methods:

  • Literature review of crotonylation research.
  • Analysis of crotonylation's involvement in various cellular processes (transcription, DNA repair, autophagy, ferroptosis).
  • Examination of crotonylation's role in cancer, immunotherapy, and diagnostics.

Main Results:

  • Crotonylation extensively modifies histones and non-histone proteins, impacting diverse cellular functions.
  • It plays a critical role in cancer, influencing metabolic reprogramming, resistance, and immune evasion.
  • Crotonylation crosstalks with other modifications (SUMOylation, ubiquitination, acetylation) to regulate genome stability.
  • Advanced chemical biology and deep learning tools enable precise detection and functional analysis.
  • Crotonylation marks show promise as diagnostic and prognostic biomarkers.

Conclusions:

  • Crotonylation is a crucial metabolite sensor with broad regulatory roles in cellular processes and disease.
  • Targeting crotonylation offers significant therapeutic potential for precision medicine in cancer.
  • Further research into crotonylation "writers", "erasers", and "readers" is warranted for clinical applications.
Keywords:
CancerCrotonylationHistone modificationMetabolic reprogrammingShort-chain acylation

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