Related Experiment Video

Updated: Dec 14, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

6.8K

Myc-mediated SDHA acetylation triggers epigenetic regulation of gene expression and tumorigenesis

Shi-Ting Li1, De Huang1, Shengqi Shen1

  • 1Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.

Nature Metabolism
|July 23, 2020
PubMed

Insights

The oncogene Myc drives cancer by deacetylating succinate dehydrogenase complex subunit A (SDHA), leading to epigenetic changes and tumor growth. This study reveals a novel Myc-driven acetylation pathway critical for cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Epigenetics
  • Oncology

Background:

  • The transcription factor c-Myc (Myc) is a key driver of tumorigenesis.
  • Myc's role in epigenetic regulation of gene expression is not fully understood.
  • Succinate dehydrogenase complex subunit A (SDHA) is involved in cellular metabolism.

Purpose of the Study:

  • To elucidate the role of Myc in epigenetic regulation via SDHA acetylation.
  • To investigate the mechanism by which Myc influences H3K4me3 activation and gene expression.
  • To determine the contribution of acetylated SDHA to tumor growth and clinical outcomes.

Main Methods:

  • Investigated Myc-mediated acetylation and degradation of SDHA.
  • Assessed the impact of SDHA deactivation on succinate levels and H3K4me3 activation.
  • Utilized in vitro and in vivo models, along with analysis of clinical samples.

Main Results:

  • Myc promotes acetylation-dependent deactivation of SDHA by activating SKP2-mediated SIRT3 degradation.
  • Inhibition of SDHA activity by Myc leads to succinate accumulation, activating H3K4me3 and tumor-specific gene expression.
  • Acetylated SDHA at Lys 335 is crucial for tumor growth, with increased tumorigenesis observed in clinical samples.

Conclusions:

  • Myc hijacks cellular metabolism and epigenetic machinery through SDHA acetylation.
  • This study reveals a novel acetylation-dependent mechanism linking Myc to H3K4me3 activation and cancer progression.
  • Targeting this pathway may offer new therapeutic strategies for Myc-driven cancers.

More Related Videos

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

6.4K
Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy07:20

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy

Published on: October 18, 2024

846

Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.6K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.1K
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
15.5K
Histone Modification02:32

Histone Modification

4.1K