Related Experiment Video
Updated: Jun 19, 2025
09:20
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
8.5K
Reversible acetylation of HDAC8 regulates cell cycle
Chaowei Sang1, Xuedong Li1, Jingxuan Liu1
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, 200438, Shanghai, China.
EMBO Reports
|July 23, 2024
Summary
Stress triggers HDAC8 acetylation at K202, a novel cell cycle regulator. This modification increases cohesin acetylation, leading to cell cycle arrest and altered gene expression, revealing a new layer of stress response.
Area of Science:
- Cell Biology
- Molecular Biology
- Epigenetics
Background:
- Histone deacetylase 8 (HDAC8) is a class I HDAC crucial for cell cycle regulation via SMC3 deacetylation.
- While cyclin-dependent kinases (CDKs) are known regulators, other mechanisms controlling the cell cycle, especially under stress, are less understood.
Purpose of the Study:
- To investigate the role of HDAC8 acetylation as a stress-responsive cell cycle regulator.
- To elucidate the functional consequences of K202 acetylation in HDAC8.
Main Methods:
- Analysis of K202 acetylation in HDAC8.
- Assessment of HDAC8 activity and SMC3 acetylation levels.
- Gene expression profiling and analysis of 3D genome structure.
- Cell cycle progression analysis.
Main Results:
- Acetylation of K202 in HDAC8, catalyzed by Tip60, inhibits HDAC8 activity.
- This inhibition leads to increased SMC3 acetylation and subsequent G2/M phase cell cycle arrest.
- Cells with K202-acetylated HDAC8 mutants show altered gene expression and enhanced chromatid loop interactions, impacting genome structure.
Conclusions:
- Reversible acetylation of HDAC8 at K202 functions as a critical stress-responsive cell cycle regulator.
- This mechanism expands the understanding of how cells respond to stress by modulating cell cycle progression and genome organization.
Related Concept Videos
02:34Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
00:50Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
02:32Histone Modification
13.2K
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...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.2K
01:32Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
02:37DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
01:23Negative Regulator Molecules
35.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K