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Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns
A Gould1, A Morrison, G Sproat
1Laboratory of Developmental Neurobiology, Medical Research Council (MRC) National Institute for Medical Research, London, UK.
Genes & Development
|April 1, 1997
Summary
Vertebrate Hox genes use shared enhancers, like CR3, to regulate overlapping expression domains. This mechanism, including a conserved Deformed/Hoxb4 autoregulatory loop, differs from Drosophila, highlighting evolutionary regulatory divergence.
Area of Science:
- Developmental Biology
- Genetics
- Evolutionary Biology
Background:
- Vertebrate Hox genes exhibit complex, nested expression patterns crucial for development.
- Overlapping expression domains are common, but the regulatory mechanisms are not fully understood.
Purpose of the Study:
- To investigate the regulatory mechanisms underlying shared expression domains of vertebrate Hox genes.
- To explore the evolutionary conservation and function of a specific enhancer element (CR3).
Main Methods:
- Transgenic analysis in mice to identify and characterize enhancer function.
- Comparative analysis of enhancer sequences and function across species, including Drosophila.
Main Results:
- A shared enhancer, CR3, was identified that specifies the overlapping expression domain of Hoxb3 and Hoxb4 in mouse hindbrain.
- CR3's position and sequence are conserved from fish to mammals, mediating transcriptional activation by multiple Hox genes.
- CR3 functions as a selective HOX response element in Drosophila, revealing a conserved Deformed/Hoxb4 autoregulatory loop.
- Positive cross-regulation and enhancer sharing reinforce vertebrate Hox gene expression overlaps, contrasting with negative cross-regulation in Drosophila.
Conclusions:
- Enhancer sharing and positive cross-regulation are key mechanisms for overlapping Hox gene expression in vertebrates.
- A Deformed/Hoxb4 autoregulatory loop is conserved between mice and Drosophila, indicating deep evolutionary roots.
- Mechanistic differences in Hox complex regulation exist between arthropods and vertebrates, despite overall conservation.