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PMID: 10398683 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The control of trunk Hox specificity and activity by Extradenticle.

Genes & development ·Vol. 13 ·No. 13 ·1999-07-01 ·Pages 1704-16

Ryoo HD, Mann RS

Abstract

We characterize a 37-bp element (fkh[250]) derived from the fork head (fkh) gene, a natural target of the Hox gene Sex combs reduced (Scr). In vitro, Scr cooperatively binds to this DNA with the Hox cofactor Extradenticle (Exd), and the activation of this enhancer in vivo requires Scr and exd. Other Hox/Exd heterodimers do not activate this element in vivo and do not bind this element with high affinity in vitro. The amino-terminal arm of the Scr homeodomain is crucial for the specific activation of this element in vivo. By mutating two base pairs within this element, we can convert the Scr/Exd-binding site to a Hox/Exd consensus site that binds several different Hox/Exd heterodimers. This element, fkh[250(con)], is activated by Scr, Antennapedia (Antp), and Ultrabithorax (Ubx) but repressed by abdominal-A (abd-A). We also show that Scr and Exd are only able to activate the fkh[250] element during the early stages of embryogenesis because, by stage 11, Scr negatively regulates the gene homothorax (hth), which is required for the nuclear localization of Exd. These results suggest that Exd is a specificity cofactor for the trunk Hox genes, and that the control of Exd subcellular localization is a mechanism to regulate Hox activity during development.

MeSH Terms
Abdomen/embryology Animals Antennapedia Homeodomain Protein DNA-Binding Proteins/physiology Dimerization Drosophila Proteins Drosophila melanogaster/embryology,genetics Embryo, Nonmammalian/ultrastructure Enhancer Elements, Genetic Forkhead Transcription Factors Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins/physiology Insect Proteins/genetics,physiology Morphogenesis/genetics Nuclear Proteins/genetics,physiology Repressor Proteins/genetics,physiology Subcellular Fractions/chemistry Transcription Factors/genetics,physiology
Chemicals
Antennapedia Homeodomain Protein Antp protein, Drosophila DNA-Binding Proteins Drosophila Proteins Forkhead Transcription Factors Homeodomain Proteins Insect Proteins Nuclear Proteins Repressor Proteins Scr protein, Drosophila Transcription Factors Ubx protein, Drosophila exd protein, Drosophila hth protein, Drosophila abd-A protein, Drosophila
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ryoo H D
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Mann R S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.13.1704
Published
1999-07-01
Pages
1704-16
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316852
Subset
IM
Grants
NIGMS NIH HHS · R01 GM054510 · United States
External Links
PubMed source DOI: 10.1101/gad.13.13.1704 PMC Full Text View journal details
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