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| Status |
Public on May 24, 2024 |
| Title |
Effect of mutation at the K202 site of the HDAC8 on 3D genomic structure in HeLa cells |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
HDAC8, a member of class I HDACs, plays a pivotal role in cell cycle regulation by deacetylating the cohesin subunit SMC3. While cyclins and CDKs are well-established cell cycle regulators, our knowledge of other regulators remains limited. Here we reveal the acetylation of K202 in HDAC8 as a key cell cycle regulator responsive to stress. K202 acetylation in HDAC8, primarily catalyzed by Tip60, restricts HDAC8 activity, leading to increased SMC3 acetylation and cell cycle arrest. Furthermore, cells expressing the mutant form of HDAC8 mimicking K202 acetylation display significant alterations in gene expression, potentially linked to changes in 3D genome structure, including enhanced chromatid loop interactions. K202 acetylation impairs cell cycle progression by disrupting the expression of cell cycle-related genes and sister chromatid cohesion, resulting in G2/M phase arrest. These findings indicate the reversible acetylation of HDAC8 as a cell cycle regulator, expanding our understanding of stress-responsive cell cycle dynamics.
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| Overall design |
To directly examine the influence of K202 acetylation on cellular processes, we harnessed CRISPR/Cas9 technology to modify the HDAC8 gene in HeLa cells. We generated the K202Q missense mutation, which mimics the acetylated state, and concurrently, we also generated the K202R mutant. Monoclonal cells were screened and confirmed for successful mutation of the HDAC8 gene through DNA sequence analysis.
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| Contributor(s) |
Sang C, Li X, Liu J, Chen Z, Xia M, Yu M, Yu W |
| Citation(s) |
39043961 |
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| Submission date |
Nov 13, 2023 |
| Last update date |
Jul 26, 2024 |
| Contact name |
Chaowei Sang |
| E-mail(s) |
chaoweisang@gmail.com
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| Organization name |
Fudan University
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| Department |
School of life science Fudan uniersity
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| Lab |
Yuwei Lab
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| Street address |
Songhu Road 2005
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| City |
Shanghai |
| State/province |
Shanghai Province |
| ZIP/Postal code |
200082 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE247611 |
Reversible acetylation of HDAC8 regulates cell cycle |
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| Relations |
| BioProject |
PRJNA1039814 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247609_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of HIC) |
SRA Run Selector |
| Raw data are available in SRA |
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