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| Status |
Public on Dec 19, 2011 |
| Title |
The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The activating E2F-transcription factors are best known for their dependence on the Retinoblastoma protein and their role in cellular proliferation. E2F3 is uniquely amplified in specific human tumours where its expression is inversely correlated with the survival of patients. Here, E2F3 interaction partners were identified by mass spectrometric analysis. We show that the SNF2-like HELLS interacts with E2F3 in vivo and cooperates with its oncogenic functions. Depletion of HELLS severely perturbs the induction of E2F-target genes, hinders cell cycle re-entry and growth. Using chromatin immmunoprecipitation coupled to sequencing we identified genome-wide targets of HELLS and E2F3. Our analysis revealed that HELLS binds near promoters of active genes, including the trithorax-related MLL1, and co-regulates E2F3-dependent genes. Our analysis is the first to link HELLS with E2F-controlled processes that are critical to establish a proliferative tumour circuitry. Strikingly, just as E2F3, HELLS is overexpressed in human tumours including prostate cancer, indicating that either factor may contribute to the malignant progression of tumours. Our work reveals that HELLS is important for E2F3 in tumour cell proliferation.
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| Overall design |
Examination of E2F3, Hells, and H3K27me3 in 2 cell types.
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| Contributor(s) |
von Eyss B, Maaskola J, Memczak S, Möllmann K, Schuetz A, Loddenkemper C, Tanh M, Otto A, Muegge K, Heinemann U, Rajewsky N, Ziebold U |
| Citation(s) |
22157815 |
| Submission date |
Nov 17, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Jonas Maaskola |
| Organization name |
Max-Delbrueck Centrum Berlin-Buch
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| Department |
Systems Biology of Gene Regulatory Elements
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| Lab |
Rajewsky
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| Street address |
Robert-Roessle Str. 10
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| City |
Berlin |
| ZIP/Postal code |
13125 |
| Country |
Germany |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (8)
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| Relations |
| SRA |
SRP009380 |
| BioProject |
PRJNA148057 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33791_RAW.tar |
296.3 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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