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| Status |
Public on Feb 12, 2014 |
| Title |
Genome-wide maps of WT and over-expressing CenH3/CENP-A in Human HeLa S3 cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Centromeres are essential to ensure proper chromosome segregation in eukaryotes. Their definition relies on the presence of a centromere-specific H3 histone variant CenH3, known as CENP-A in mammals. Its overexpression in aggressive cancers raises questions concerning its effect on chromatin dynamics and contribution to tumorigenesis. We find that CenH3 overexpression in human cells leads to ectopic enrichment at sites of active histone turnover. Furthermore, in over-expressing conditions, we see the formation of a novel heterotypic particle (CenH3-H4/H3.3-H4) that occludes CTCF binding, but this occlusion has only a minor effect on gene expression. Ectopic localization and CTCF occlusion depends on the H3.3 chaperone DAXX, rather than its dedicated chaperone HJURP. This DAXX-dependent occlusion also occurs in naturally overexpressing cancer cells. Furthermore, our cellular model reveals a DAXX-dependent survival advantage when challenged by DNA damage. Our findings illustrate how changes in histone variant levels can disrupt chromatin dynamics in disease and provides a possible mechanism for cell resistance to anti-cancer treatments.
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| |
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| Overall design |
Examination of CenH3 ChIP-seq and RNA-seq transcriptional programs in two conditions - WT and CenH3 over-expressing.
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| |
|
| Contributor(s) |
Woolfe A, Lacoste N, Almouzni G |
| Citation(s) |
24530302 |
| Submission date |
Dec 17, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Genevieve Almouzni |
| E-mail(s) |
genevieve.almouzni@curie.fr, adam.woolfe@curie.fr
|
| Phone |
+33156246701
|
| Organization name |
Institut Curie
|
| Department |
Nuclear Dynamics and Genome Plasticity
|
| Lab |
Chromatin dynamics
|
| Street address |
26 Rue D'Ulm
|
| City |
Paris |
| State/province |
Ille De France |
| ZIP/Postal code |
75005 |
| Country |
France |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (16)
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|
| Relations |
| BioProject |
PRJNA183936 |
| SRA |
SRP017577 |
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