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| Status |
Public on Jan 08, 2014 |
| Title |
CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Eukaryotic gene regulation implies that transcription factors gain access to genomic information via poorly understood processes involving activation and targeting of kinases, histone-modifying enzymes, and chromatin remodelers to chromatin. Here we report that progestin gene regulation in breast cancer cells requires a rapid and transient increase in poly-(ADP)-ribose (PAR), accompanied by a dramatic decrease of cellular NAD that could have broad implications in cell physiology. This rapid increase in nuclear PARylation is mediated by activation of PAR polymerase PARP-1 as a result of phosphorylation by cyclin-dependent kinase CDK2. Hormone-dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities. Activated PARP-1 contributes to the displacement of histone H1 and is essential for regulation of the majority of hormone-responsive genes and for the effect of progestins on cell cycle progression. Both global chromatin immunoprecipitation (ChIP) coupled with deep sequencing (ChIP-seq) and gene expression analysis show a strong overlap between PARP-1 and CDK2. Thus, progestin gene regulation involves a novel signaling pathway that connects CDK2-dependent activation of PARP-1 with histone H1 displacement. Given the multiplicity of PARP targets, this new pathway could be used for the pharmacological management of breast cancer.
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| Overall design |
PARP-1 activation mechanism by CDK2 in response of progestin in breast cancer cells
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| Contributor(s) |
Wright RG, Castellano G, Bonet J, Le Dilly F, Font-Mateu J, Ballaré C, Nacht AS, Soronellas D, Oliva B, Beato M |
| Citation(s) |
27257257 |
| Submission date |
Jan 07, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Miguel Beato |
| E-mail(s) |
miguel.beato@crg.eu
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| Organization name |
CRG
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| Street address |
Aiguader 88
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| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA233576 |
| SRA |
SRP035158 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE53855_readCounts_all_samples.txt.gz |
4.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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