Related Experiment Video

Updated: Aug 30, 2025

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
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Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

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Elevated levels of the methyltransferase SETD2 causes transcription and alternative splicing changes resulting in

Saikat Bhattacharya1, Divya Reddy1, Ning Zhang1

  • 1Stowers Institute for Medical Research, Kansas City, MO, United States.

Frontiers in Cell and Developmental Biology
|August 29, 2022
PubMed

Insights

High levels of the SETD2 protein paradoxically promote cancer progression by disrupting histone marks and upregulating cell cycle pathways. Proteasome-mediated degradation of SETD2 is crucial for its tumor suppressor function.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • The methyltransferase SETD2 is critical for regulating gene expression, splicing, and DNA repair.
  • SETD2 mutations are found in various cancers, suggesting a tumor suppressor role.
  • SETD2 is tightly regulated by proteasomal degradation, maintaining low endogenous levels.

Purpose of the Study:

  • To investigate the consequences of SETD2 accumulation on its epigenetic functions and cellular phenotypes.
  • To understand the role of SETD2 proteolysis in maintaining its tumor-suppressive activity.

Main Methods:

  • Analysis of H3K36me3 histone mark deposition upon SETD2 accumulation.
  • Assessment of global transcription and alternative splicing changes.
  • Evaluation of cell proliferation and migration phenotypes.

Main Results:

  • SETD2 accumulation leads to aberrant H3K36me3 deposition, with reduced enrichment over gene bodies and exons.
  • Perturbed epigenetic landscape alters transcription and alternative splicing.
  • Excessive SETD2 upregulates cell cycle pathways, increasing proliferation and migration.

Conclusions:

  • SETD2 proteolysis is essential for maintaining its proper function and epigenetic fidelity.
  • Dysregulation of SETD2 levels can paradoxically promote cancer progression, challenging its established tumor suppressor role.
Keywords:
cancerchromatinepigeneticshistonemethylation

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