Genome-Wide Analysis of the Binding of the Hox Protein Ultrabithorax and the Hox Cofactor Homothorax in Drosophila

@article{Choo2011GenomeWideAO,
  title={Genome-Wide Analysis of the Binding of the Hox Protein Ultrabithorax and the Hox Cofactor Homothorax in Drosophila},
  author={Siew Woh Choo and Robert White and Steven Russell},
  journal={PLoS ONE},
  year={2011},
  volume={6}
}
Hox genes encode a family of transcription factors that are key developmental regulators with a highly conserved role in specifying segmental diversity along the metazoan body axis. Although they have been shown to regulate a wide variety of downstream processes, direct transcriptional targets have been difficult to identify and this has been a major obstacle to our understanding of Hox gene function. We report the identification of genome-wide binding sites for the Hox protein Ultrabithorax… 

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References

SHOWING 1-10 OF 91 REFERENCES

Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites.

It is proposed that the regulation of some Hox target genes evolves via the accumulation of multiple Hox monomer binding sites, and this mode of target gene regulation appears to be important for distal appendage development and the evolution of appendage diversity.

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

Analysis of the Hox gene Ultrabithorax in Drosophila melanogaster reveals that Ubx target genes are largely distinct at different stages of appendage morphogenesis, suggesting extensive interactions between Hox genes and hormone-controlled regulatory networks to orchestrate complex genetic programs during metamorphosis.

Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene.

This work identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm, and proposes that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.

A structural model for a homeotic protein-extradenticle-DNA complex accounts for the choice of HOX protein in the heterodimer.

  • S. ChanR. Mann
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
Analysis of protein-DNA interactions that are important for forming the labial-extradenticle-DNA complex demonstrates that extradenticle prefers to bind cooperatively with different HOX proteins depending on subtle differences in the heterodimer binding site.

Collaboration between Smads and a Hox protein in target gene repression

This work finds that two Smad proteins, effectors of the Drosophila Dpp/TGF-β pathway, that are genetically required for the activation of the spalt (sal) gene in the wing, collaborate with the Hox protein Ultrabithorax (Ubx) to directly repress sal in the haltere.

Comparative analysis of Hox downstream genes in Drosophila

This work quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants, providing a framework for the morphogenesis of the maxillary segment.

Shaping segments: Hox gene function in the genomic age

  • S. D. HueberI. Lohmann
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2008
The role of Hox genes in shaping segmental morphologies along the AP axis in Drosophila is focused on, some of the conclusions drawn from analyses of large target gene sets are discussed and methods that could be used to gain a more thorough understanding of H Cox molecular function are highlighted.

Stability and Dynamics of Polycomb Target Sites in Drosophila Development

The analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription, and shows that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding.

Hox specificity unique roles for cofactors and collaborators.

...