Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells

doi:10.1128/MCB.21.10.3589-3597.2001

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Molecular and Cellular Biology, May 2001, p. 3589-3597, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3589-3597.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells

Keri Fair,¹ Melanie Anderson,¹ Elena Bulanova,¹ Huaifeng Mi,² Maximilian Tropschug,² and Manuel O. Diaz¹^,^*

Cancer Center, Medical Center, Loyola University $---$ Chicago, Maywood, Illinois 60153,¹ and Institut für Biochemie und Molekularbiologie der Universität Freiburg, D-79104 Freiburg, Germany²

Received 29 June 2000/Returned for modification 29 August 2000/Accepted 15 February 2001

The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their functionis unknown. We have determined that these fingers mediate homodimerizationand binding of MLL to Cyp33, a nuclear cyclophilin. These twoproteins interact in vitro and in vivo in mammalian cells andcolocalize at specific nuclear subdomains. Overexpression of theCyp33 protein in leukemia cells results in altered expressionof HOX genes that are targets for regulation by MLL. These alterationsare suppressed by cyclosporine and are not observed in cell linesthat express a mutant MLL protein without PHD fingers. These resultssuggest that binding of Cyp33 to MLL modulates its effects onthe expression of targetgenes.

^* Corresponding author. Mailing address: Loyola University Medical Center, Cancer Center Bldg. 112, Rm. 333, 2160 South FirstAve., Maywood, IL 60153. Phone: (708) 327-3172. Fax: (708) 327-3342.E-mail: mdiaz2{at}lumc.edu.

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