The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation

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.