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Molecular and Cellular Biology, April 2002, p. 2687-2702, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2687-2702.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Sp100 Interacts with ETS-1 and Stimulates Its Transcriptional Activity

Christine Wasylyk, Sophie E. Schlumberger,,{dagger} Paola Criqui-Filipe, and Bohdan Wasylyk*

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch Cedex, France

Received 24 July 2001/ Returned for modification 10 September 2001/ Accepted 4 January 2002

The cell nucleus is highly organized into distinct domains that spatially separate physiological processes. One of these domains, the Sp100-promyelocytic leukemia protein nuclear body (NB), is implicated in pathological processes, such as cancer and viral infection, yet its functions remain poorly understood. We show here that Sp100 interacts physically and functionally with ETS-1 and that NB morphology is affected by ETS-1. ETS-1 is a member of the ets family of transcription factors, which are key mediators of physiological and pathological processes. We have found that Sp100 interacts with two regions of ETS-1 (domains A+B and D+E+F). ETS-1 alters NBs while remaining localized throughout the nucleus, apparently by recruitment of the core component Sp100 away from the NBs. Sp100 strongly increases ETS-1 activation of natural and ets-focused promoters, through a mechanism involving the activation (C) domain of ETS-1 in addition to the interaction domains. Sp100 acts as a novel coactivator that potentiates the activator function of ETS-1. Our results provide an important new connection between nuclear structures and an important regulator of gene expression.

* Corresponding author. Mailing address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 163, CNRS/INSERM/ULP, 67404 Illkirch Cedex, France. Phone: 33 (0) 3-88-65-34-11. Fax: 33 (0) 3-88-65-32-01. E-mail: boh{at}igbmc.u-strasbg.fr.

{dagger} Present address: Department of Research, University Hospital, CH-4031 Basel, Switzerland.

Molecular and Cellular Biology, April 2002, p. 2687-2702, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2687-2702.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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