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| Status |
Public on Jul 16, 2020 |
| Title |
CENP-A overexpression promotes aneuploidy and karyotypic heterogeneity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Centromeric localization of the evolutionarily conserved histone H3 variant, CENP-A. is essential for chromosomal stability. CENP-A overexpression (OE) causesd its mislocalization to non-centromeric regions resulting in chromosomal instability (CIN) in yeast, flies and human cells. CENP-A OE and mislocalization have been observed in cancers and correlates with poor prognosis. However, the molecular consequences of CENP-A OE on CIN and aneuploidy have not been defined. Here, we overexpressed YFP-CENP-A in a pseudodiploid DLD1 cell line and showed that CENP-A OE leads to its mislocalization and CIN due to defects in kinetochore integrity and kinetochore-microtubule attachments. CENP-A OE also leads to its mislocalization and CIN in a xenograft mouse model. Under these conditions, it contributes to aneuploidy with karyotypic heterogeneity in human cells and xenograft mouse model. In summary, our studies provide a molecular link between CENP-A OE and aneuploidy, and suggest that karyotypic heterogeneity may contribute to the aggressive phenotype of CENP-A overexpressing cancers.
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| Overall design |
Three biological replicates were analyzed for each of two conditions
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| Contributor(s) |
Shrestha RL, Hogan AK, Foltz DR, Basrai MA |
| Citation missing |
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| |
| Submission date |
Jul 15, 2020 |
| Last update date |
Sep 11, 2020 |
| Contact name |
Daniel Foltz |
| Organization name |
Northwestern University
|
| Street address |
303 E Superior St
|
| City |
Chicago |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA646383 |
| SRA |
SRP272031 |
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