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Series GSE154460 Query DataSets for GSE154460
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
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.
 
Overall design Three biological replicates were analyzed for each of two conditions
 
Contributor(s) Shrestha RL, Hogan AK, Foltz DR, Basrai MA
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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
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (6)
GSM4671404 MB07
GSM4671405 MB08
GSM4671406 MB09
Relations
BioProject PRJNA646383
SRA SRP272031

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Supplementary file Size Download File type/resource
GSE154460_CAyfp+d_v_-d.htseq.edgeR.txt.gz 1.7 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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