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Molecular and Cellular Biology, November 1998, p. 6201-6212, Vol. 18, No. 11
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.
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

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