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(De)Toxifying the Epigenetic Code.

Qingfei Zheng1, Nicholas A Prescott1,2, Igor Maksimovic1,2

  • 1Chemical Biology Program , Memorial Sloan Kettering Cancer Center , New York 10044 , New York , United States.

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|March 7, 2019
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This summary is machine-generated.

Reactive chemicals modify proteins, leading to disease. This review explores non-enzymatic covalent modifications (NECMs) on histones, crucial for gene regulation, and their toxicological impact on the epigenome.

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Area of Science:

  • Cellular Biology
  • Epigenetics
  • Toxicology

Background:

  • Cells encounter endogenous and exogenous reactive chemical species.
  • These species cause non-enzymatic covalent modifications (NECMs) on proteins, altering their function.
  • NECMs accumulate and are implicated in diseases like Alzheimer's, cancer, and diabetes.

Purpose of the Study:

  • To review the impact of NECMs on the epigenetic landscape.
  • To explore the role of NECMs on histones in gene regulation and cellular fate.
  • To discuss the implications of NECMs in disease pathogenesis.

Main Methods:

  • Review of existing literature on NECMs and histone modifications.
  • Analysis of the mechanisms by which NECMs affect protein function.
  • Discussion of the challenges in studying NECMs in vivo.

Main Results:

  • Histones, with long half-lives, are susceptible to NECMs.
  • NECMs on histones can influence gene transcription, a process typically regulated enzymatically.
  • The epigenetic code can be directly altered by chemical exposure.

Conclusions:

  • NECMs on histones represent a poorly understood area of epigenetics.
  • Understanding NECMs is crucial for comprehending disease mechanisms.
  • Cellular detoxification mechanisms counteract chemical-induced epigenetic alterations.