|
| Status |
Public on Sep 24, 2024 |
| Title |
CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [CHIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Maintaining centromere integrity is crucial for genome stability and proper chromosome segregation during mitosis. CENPA, a conserved histone H3 variant, is localized at the centromeres and plays an essential role in preserving centromere integrity and function. However, the mechanisms that retain CENPA at centromeres remain an enigma. In this study, we identified CENPA as an m6A reader of centromeric RNA (cenRNA), which is essential for its centromeric localization and function in maintaining centromere stability. We discovered a higher level of m6A modification on cenRNA in cancerous cells compared to normal cells. CENPA preferentially binds the cenRNAs with m6A modification, which stabilizes its localization in centromeric regions during the S phase of the cell cycle. We then identified two residues in CENPA responsible for m6A recognition. Mutations in these CENPA residues or removal of m6A on cenRNAs leads to the loss of centromere-bound CENPA during the S phase, thereby resulting in abnormal chromosome separation during mitosis and increased genomic instability. Consequently, this impairment in centromere integrity hindered cancer cell proliferation and tumor growth. Our findings unveiled a novel m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potentially new targets for cancer therapy.
|
| |
|
| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3.3 and CENPA during the S phase of A375 cells upon METTL3 knockdown or with dCas13b-FTO targeting.
|
| |
|
| Contributor(s) |
Kang Z, Li R, Liu J |
| Citation(s) |
39305902 |
| |
| Submission date |
Apr 28, 2023 |
| Last update date |
Sep 25, 2024 |
| Contact name |
Jun Liu |
| E-mail(s) |
junliu1223@pku.edu.cn
|
| Organization name |
Peking University
|
| Department |
School of Life Sciences
|
| Street address |
Haidian District
|
| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (34)
|
|
| This SubSeries is part of SuperSeries: |
| GSE230880 |
m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells |
|
| Relations |
| BioProject |
PRJNA962903 |
Less...
More...