Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell Biol
1998 Nov 01;1811:6201-12. doi: 10.1128/MCB.18.11.6201.
Show Gene links
Show Anatomy links
Definition of the transcriptional activation domains of three human HOX proteins depends on the DNA-binding context.
Viganò MA
,
Di Rocco G
,
Zappavigna V
,
Mavilio F
.
???displayArticle.abstract???
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.
Acampora,
The human HOX gene family.
1989,
Pubmed
Ananthan,
Synergistic activation of transcription is mediated by the N-terminal domain of Drosophila fushi tarazu homeoprotein and can occur without DNA binding by the protein.
1993,
Pubmed
Annweiler,
Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity.
1992,
Pubmed
Arcioni,
The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins.
1992,
Pubmed
Berthelsen,
The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity.
1998,
Pubmed
Chan,
The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences.
1993,
Pubmed
Chang,
Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins.
1995,
Pubmed
Copeland,
Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide.
1996,
Pubmed
Di Rocco,
Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex.
1997,
Pubmed
,
Xenbase
Fitzpatrick,
Homeodomain-independent activity of the fushi tarazu polypeptide in Drosophila embryos.
1992,
Pubmed
Gehring,
Homeodomain-DNA recognition.
1994,
Pubmed
Gerster,
The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription.
1990,
Pubmed
Gibson,
The specificities of Sex combs reduced and Antennapedia are defined by a distinct portion of each protein that includes the homeodomain.
1990,
Pubmed
Gould,
Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns.
1997,
Pubmed
,
Xenbase
Guazzi,
The thyroid transcription factor-1 gene is a candidate target for regulation by Hox proteins.
1994,
Pubmed
,
Xenbase
Guichet,
The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors.
1997,
Pubmed
Hayashi,
What determines the specificity of action of Drosophila homeodomain proteins?
1990,
Pubmed
Knoepfler,
The pentapeptide motif of Hox proteins is required for cooperative DNA binding with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1.
1995,
Pubmed
Krumlauf,
Hox genes in vertebrate development.
1994,
Pubmed
Kuziora,
A homeodomain substitution changes the regulatory specificity of the deformed protein in Drosophila embryos.
1989,
Pubmed
Lu,
Heterodimerization of Hox proteins with Pbx1 and oncoprotein E2a-Pbx1 generates unique DNA-binding specifities at nucleotides predicted to contact the N-terminal arm of the Hox homeodomain--demonstration of Hox-dependent targeting of E2a-Pbx1 in vivo.
1997,
Pubmed
Lutz,
Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved.
1996,
Pubmed
Maconochie,
Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1.
1997,
Pubmed
Malicki,
Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae.
1990,
Pubmed
Malicki,
Functional analysis of the mouse homeobox gene HoxB9 in Drosophila development.
1993,
Pubmed
Manak,
Gene regulation: able assistants for homeodomain proteins.
1993,
Pubmed
Mann,
The specificity of homeotic gene function.
1995,
Pubmed
Mann,
Functional dissection of Ultrabithorax proteins in D. melanogaster.
1990,
Pubmed
Mann,
Extra specificity from extradenticle: the partnership between HOX and PBX/EXD homeodomain proteins.
1996,
Pubmed
McGinnis,
Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in Drosophila embryos and larvae.
1990,
Pubmed
Phelan,
Cooperative interactions between HOX and PBX proteins mediated by a conserved peptide motif.
1995,
Pubmed
Pöpperl,
Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.
1995,
Pubmed
Pöpperl,
An autoregulatory element of the murine Hox-4.2 gene.
1992,
Pubmed
Rambaldi,
A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2).
1994,
Pubmed
Sadowski,
GAL4-VP16 is an unusually potent transcriptional activator.
1988,
Pubmed
Saffman,
A differential response element for the homeotics at the Antennapedia P1 promoter of Drosophila.
1994,
Pubmed
Schier,
Functional specificity of the homeodomain protein fushi tarazu: the role of DNA-binding specificity in vivo.
1993,
Pubmed
Schnabel,
Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues.
1996,
Pubmed
Sreenath,
Functional specificity of Hoxa-4 in vertebral patterning lies outside of the homeodomain.
1996,
Pubmed
Triezenberg,
Structure and function of transcriptional activation domains.
1995,
Pubmed
Yu,
The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz.
1997,
Pubmed
Zappavigna,
HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities.
1991,
Pubmed
Zappavigna,
HMG1 interacts with HOX proteins and enhances their DNA binding and transcriptional activation.
1996,
Pubmed
Zappavigna,
Specificity of HOX protein function depends on DNA-protein and protein-protein interactions, both mediated by the homeo domain.
1994,
Pubmed
Zawel,
Common themes in assembly and function of eukaryotic transcription complexes.
1995,
Pubmed
Zeng,
Ectopic expression and function of the Antp and Scr homeotic genes: the N terminus of the homeodomain is critical to functional specificity.
1993,
Pubmed
Zhao,
The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.
1993,
Pubmed
Zhao,
Functional dissection of the mouse Hox-a5 gene.
1996,
Pubmed
