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PMID: 22157815 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 31 ·No. 4 ·2012-02-15 ·Pages 972-85

von Eyss B, Maaskola J, Memczak S, Möllmann K, Schuetz A, Loddenkemper C, Tanh MD, Otto A, Muegge K, Heinemann U, Rajewsky N, Ziebold U

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.

MeSH Terms
Cell Cycle Cell Transformation, Neoplastic Chromatin Immunoprecipitation DNA Helicases/metabolism,physiology E2F3 Transcription Factor/physiology Humans Male Prostatic Neoplasms/pathology Protein Binding Transcription, Genetic/physiology
Chemicals
E2F3 Transcription Factor E2F3 protein, human DNA Helicases HELLS protein, human
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
von Eyss Björn
Cancer Research, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany.
Maaskola Jonas
Memczak Sebastian
Möllmann Katharina
Schuetz Anja
Loddenkemper Christoph
Tanh Mai-Dinh
Otto Albrecht
Muegge Kathrin
Heinemann Udo
Rajewsky Nikolaus
Ziebold Ulrike
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2011.451
Published
2012-02-15
Epub
2011-00-13
Pages
972-85
Language
English
Region
England
NLM ID
8208664
PMCID
PMC3280551
Subset
IM
External Links
PubMed source DOI: 10.1038/emboj.2011.451 PMC Full Text View journal details
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