title: The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation.
abstract: 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, E2F3B interaction partners were identified by mass spectrometric analysis. We show that the SNF2-like helicase HELLS interacts with E2F3A 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 E2F3A/B. HELLS binds promoters of active genes, including the trithorax-related MLL1, and co-regulates E2F3-dependent genes. 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.
authors.affiliation: Cancer Research, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: von Eyss
authors.forename: Jonas
authors.initials: J
authors.lastname: Maaskola
authors.forename: Sebastian
authors.initials: S
authors.lastname: Memczak
authors.forename: Katharina
authors.initials: K
authors.lastname: Möllmann
authors.forename: Anja
authors.initials: A
authors.lastname: Schuetz
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Mai-Dinh
authors.initials: MD
authors.lastname: Tanh
authors.forename: Albrecht
authors.initials: A
authors.lastname: Otto
authors.forename: Kathrin
authors.initials: K
authors.lastname: Muegge
authors.forename: Udo
authors.initials: U
authors.lastname: Heinemann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rajewsky
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ziebold
mesh_terms: D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000378:metabolism / Q000502:physiology*; D050699:E2F3 Transcription Factor / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D011485:Protein Binding; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D004265:DNA Helicases; C412063:HELLS protein, human