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Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling.

Minjung Lee1, Jia Li1, Yi Liang2

  • 1Centre for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University , 2121 W Holcombe Boulevard, Houston, Texas 77030, United States.

Journal of the American Chemical Society
|March 16, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed a controllable split-TET2 enzyme for temporal control of DNA oxidation. This tool helps study epigenetics and the link between DNA hydroxymethylation and chromatin accessibility in mammals.

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Area of Science:

  • Epigenetics and Molecular Biology
  • DNA modification and demethylation pathways

Background:

  • The Ten-eleven translocation (TET) enzyme family is crucial for active DNA demethylation by oxidizing 5-methylcytosine (5mC).
  • Understanding the dynamic regulation of 5mC oxidation and its impact on cellular processes is essential.

Purpose of the Study:

  • To engineer a chemically inducible split-TET2 system for precise temporal control over 5mC oxidation in mammalian cells.
  • To investigate the relationship between DNA hydroxymethylation dynamics and chromatin accessibility.

Main Methods:

  • Engineering a split-TET2 enzyme system allowing for inducible activation.
  • Utilizing the system to manipulate 5mC oxidation levels in mammalian cells.
  • Assessing the correlation between induced DNA hydroxymethylation and changes in chromatin accessibility.

Main Results:

  • Successful development of a temporally controlled split-TET2 system.
  • Demonstration of the system's ability to induce 5mC oxidation and subsequent epigenetic remodeling.
  • Evidence supporting a correlation between DNA hydroxymethylation and chromatin accessibility.

Conclusions:

  • The chemically inducible split-TET2 system provides a powerful tool for studying epigenome dynamics.
  • This technology enables the investigation of genotype-phenotype relationships without genetic alteration.
  • The tool has broad applications in interrogating cellular systems and biological processes.