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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation
Björn von Eyss1, Jonas Maaskola, Sebastian Memczak
1Cancer Research, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
The EMBO Journal
|December 14, 2011
Summary
The helicase HELLS protein interacts with E2F3A and supports its oncogenic functions in human tumors. Depleting HELLS hinders tumor cell proliferation, highlighting its role in cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- E2F transcription factors regulate cell proliferation and are linked to cancer.
- E2F3 amplification in tumors correlates with poor patient survival.
- The Retinoblastoma protein (Rb) typically controls E2F activity.
Purpose of the Study:
- To identify E2F3B interaction partners.
- To investigate the role of the helicase HELLS in E2F3-mediated oncogenesis.
- To determine the genome-wide targets of HELLS and E2F3.
Main Methods:
- Mass spectrometry to identify protein interactions.
- In vivo interaction studies between HELLS and E2F3A.
- Chromatin immunoprecipitation coupled with sequencing (ChIP-seq) for genome-wide target identification.
- Gene silencing techniques to assess HELLS function.
Main Results:
- HELLS (SNF2-like helicase) interacts with E2F3A.
- HELLS depletion impairs E2F-target gene induction, cell-cycle re-entry, and tumor cell growth.
- HELLS binds active gene promoters, including MLL1, and co-regulates E2F3 targets.
- Both E2F3 and HELLS are overexpressed in human tumors, including prostate cancer.
Conclusions:
- HELLS cooperates with E2F3A in promoting oncogenic functions.
- HELLS is crucial for E2F3-driven tumor cell proliferation.
- The overexpression of HELLS and E2F3 in tumors suggests their contribution to malignant progression.
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