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The periodic down regulation of Cyclin E gene expression from exit of mitosis to end of G1 is controlled by a deacetylase- and E2F-associated bipartite repressor element

Oncogene volume 20, pages 4115–4127 (2001)Cite this article

Abstract

The expression of cyclin E and that of a few other bona fide cell cycle regulatory genes periodically oscillates every cycle in proliferating cells. Although numerous experiments have documented the role of E2F sites and E2F activities in the control of these genes as cells exit from G0 to move through the initial G1/S phase transition, almost nothing is known on the role of E2Fs during the subsequent cell cycles. Here we show that a variant E2F-site that is part of the Cyclin E Repressor Module (CERM) (Le Cam et al., 1999b) accounts for the periodic down regulation of the cyclin E promoter observed between the exit from mitosis until the mid/late G1 phase in exponentially cycling cells. This cell cycle-dependent repression correlates with the periodic binding of an atypical G1-specific high molecular weight p107-E2F complex (Cyclin E Repressor Complex: CERC2) that differs in both size and DNA binding behaviors from known p107-E2F complexes. Notably, affinity purified CERC2 displays a TSA-sensitive histone deacetylase activity and, consistent with this, derepression of the cyclin E promoter by trichostatin A depends on the CERM element. Altogether, this shows that the cell cycle-dependent control of cyclin E promoter in cycling cells is embroiled in acetylation pathways via the CERM-like E2F element.

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Acknowledgements

This work was funded by grants from the french CNRS (ATIPE n°3), from ‘l'Association pour la Recherche contre le Cancer (ARC)’, from ‘La Ligue Contre le Cancer’ and from the ‘Human Frontier in Science Program’. J Polanowska was supported by a Boehringer Ingelheim doctoral fellowship and L Le Cam by a predoctoral fellowship from La ligue Contre le Cancer. We are grateful to Dr E Schwob for precious help on developing centrifugal elutriation, Dr O Coux and F Martin for help to purify CERC, and to Dr C Murchardt and J De Caprio for reagents. We would like to express special thanks to B Hipskind, JM Blanchard, L Dirick and A Le Cam for critical reading of the manuscript.

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  1. Institut de Genetique Moleculaire UMR 5535 / IFR24 CNRS, 1919 Route de Mende 34293, Montpellier cedex 5, France

    Jolanta Polanowska, Eric Fabbrizio, Laurent Le Cam & Claude Sardet

  2. Institut de Genetique Humaine UPR 1142 - CNRS 141, rue de la Cardonille 34396 Montpellier cedex 5, France

    Stephane Emiliani

  3. LBME IBCG CNRS 118, Route de Narbonne 31062 Toulouse cedex, France

    Didier Trouche

  4. Department of Molecular and Cellular Biology, Baylor College of Medecine, Houston, 77030, Texas, TX, USA

    Raphael Herrera

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Polanowska, J., Fabbrizio, E., Le Cam, L. et al. The periodic down regulation of Cyclin E gene expression from exit of mitosis to end of G1 is controlled by a deacetylase- and E2F-associated bipartite repressor element. Oncogene 20, 4115–4127 (2001). https://doi.org/10.1038/sj.onc.1204514

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