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Molecular and Cellular Biology, June 1999, p. 3931-3939, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Activity of Mammalian brm/SNF2alpha Is Dependent on a High-Mobility-Group Protein I/Y-Like DNA Binding Domain

Brigitte Bourachot, Moshe Yaniv,* and Christian Muchardt

Unité des Virus Oncogènes, URA1644 du CNRS, Département des Biotechnologies, Institut Pasteur, Paris, France

Received 2 December 1998/Returned for modification 13 January 1999/Accepted 26 February 1999

The mammalian SWI-SNF complex is a chromatin-remodelling machinery involved in the modulation of gene expression. Its activity relies on two closely related ATPases known as brm/SNF2alpha and BRG-1/SNF2beta . These two proteins can cooperate with nuclear receptors for transcriptional activation. In addition, they are involved in the control of cell proliferation, most probably by facilitating p105Rb repression of E2F transcriptional activity. In the present study, we have examined the ability of various brm/SNF2alpha deletion mutants to reverse the transformed phenotype of ras-transformed fibroblasts. Deletions within the p105Rb LXCXE binding motif or the conserved bromodomain had only a moderate effect. On the other hand, a 49-amino-acid segment, rich in lysines and arginines and located immediately downstream of the p105Rb interaction domain, appeared to be essential in this assay. This region was also required for cooperation of brm/SNF2alpha with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome. The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2alpha to chromatin.

* Corresponding author. Mailing address: Unité des Virus Oncogènes, Département des Biotechnologies, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33 (0)1 45 68 8513. Fax: 33 (0)1 45 68 8790. E-mail: yaniv{at}pasteur.fr.

Molecular and Cellular Biology, June 1999, p. 3931-3939, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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