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Molecular and Cellular Biology, November 1998, p. 6201-6212, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Definition of the Transcriptional Activation Domains of Three Human HOX Proteins Depends on the DNA-Binding Context

Maria Alessandra Viganò,dagger Giuliana Di Rocco, Vincenzo Zappavigna, and Fulvio Mavilio*

TIGET, Istituto Scientifico H.S. Raffaele, 20132 Milan, Italy

Received 15 May 1998/Returned for modification 18 June 1998/Accepted 12 July 1998

Hox proteins control developmental patterns and cell differentiation in vertebrates by acting as positive or negative regulators of still unidentified downstream target genes. The homeodomain and other small accessory sequences encode the DNA-protein and protein-protein interaction functions which ultimately dictate target recognition and functional specificity in vivo. The effector domains responsible for either positive or negative interactions with the cell transcriptional machinery are unknown for most Hox proteins, largely due to a lack of physiological targets on which to carry out functional analysis. We report the identification of the transcriptional activation domains of three human Hox proteins, HOXB1, HOXB3, and HOXD9, which interact in vivo with the autoregulatory and cross-regulatory enhancers of the murine Hoxb-1 and human HOXD9 genes. Activation domains have been defined both in a homologous context, i.e., within a HOX protein binding as a monomer or as a HOX-PBX heterodimer to the specific target, and in a heterologous context, after translocation to the yeast Gal4 DNA-binding domain. Transfection analysis indicates that activation domains can be identified in different regions of the three HOX proteins depending on the context in which they interact with the DNA target. These results suggest that Hox proteins may be multifunctional transcriptional regulators, interacting with different cofactors and/or components of the transcriptional machinery depending on the structure of their target regulatory elements.


* Corresponding author. Mailing address: TIGET-H.S. Raffaele, Via Olgettina, 58, 20132 Milan, Italy. Phone: 39-2-26434701. Fax: 39-2-26434827. E-mail: f.mavilio{at}hsr.it.

dagger Present address: Department of Cell Biology, Biozentrum der Uni Basel, 4056-Basel, Switzerland.


Molecular and Cellular Biology, November 1998, p. 6201-6212, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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