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

Item Type:Article
Title:The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation
Creators Name:von Eyss, B. and Maaskola, J. and Memczak, S. and Möllmann, K. and Schuetz, A. and Loddenkemper, C. and Tanh, M.D. and Otto, A. and Muegge, K. and Heinemann, U. and Rajewsky, N. and 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.
Keywords:Cell-Cycle Re-Entry, E2F3, HELLS, H3K27me3, Prostate Tumour
Source:EMBO Journal
Publisher:Nature Publishing Group
Page Range:972-985
Date:15 February 2012
Official Publication:https://doi.org/10.1038/emboj.2011.451
PubMed:View item in PubMed

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