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Developmental regulation of beta-globin gene switching
1Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60201.
Cell
|October 7, 1988
Summary
A chicken beta-globin enhancer normally regulates gene expression. However, it inappropriately activates embryonic epsilon-globin in adult cells, indicating a need for specific regulatory elements for proper gene control.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- A chicken erythroid cell-specific enhancer exists between adult beta- and embryonic epsilon-globin genes.
- The beta-globin enhancer influences transcription of both globin genes.
Purpose of the Study:
- To investigate the regulatory role of the beta-globin enhancer on both embryonic and adult globin genes.
- To understand the mechanism of stage-specific gene regulation in erythroid cells.
Main Methods:
- Analysis of deletion and substitution mutants.
- Assessing gene expression of beta- and epsilon-globin genes.
- Plasmid-based gene expression studies.
Main Results:
- The beta-globin enhancer stimulates transcription of both epsilon- and beta-globin genes.
- Epsilon-globin is inappropriately expressed in both embryonic and adult red blood cells when regulated by the beta-globin enhancer alone.
- Stage-specific regulation is achieved when both genes are on a single plasmid.
- The adult beta-globin promoter contains a developmental stage selector element (SSE).
Conclusions:
- Beta-globin tissue- and developmental stage-specific regulation depends on the interaction between the beta-globin enhancer and the SSE within the adult beta-globin promoter.
- Proper regulation of globin gene expression requires specific promoter elements to ensure appropriate temporal and tissue-specific expression.
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