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Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic
M Trudel1, J Magram, L Bruckner
1Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Molecular and Cellular Biology
|November 1, 1987
Summary
Regulatory elements control the stage-specific expression of human globin genes during development. Upstream G gamma-globin and downstream beta-globin sequences are crucial for differential gene activation in erythroid cells.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Hematology
Background:
- Human G gamma-globin and beta-globin genes exhibit stage-specific expression during development.
- Previous studies demonstrated differential expression of these globin genes in transgenic mice.
Purpose of the Study:
- To investigate the regulatory elements responsible for differential stage-specific expression of G gamma-globin and beta-globin genes.
- To analyze hybrid globin genes in transgenic mice to identify key regulatory sequences.
Main Methods:
- Construction and analysis of transgenic mice carrying various hybrid globin genes.
- Comparison of gene expression patterns between hybrid and intact globin transgenes.
- Identification of essential upstream and downstream regulatory sequences.
Main Results:
- Hybrid 5'G gamma/3'beta globin genes with G gamma-globin upstream sequences showed embryonic expression.
- Beta-globin upstream sequences were insufficient for adult erythroid cell expression.
- Beta-globin downstream sequences activated a 5'G gamma/3'beta hybrid globin gene in fetal and adult erythroid cells.
Conclusions:
- Positive regulatory elements upstream of G gamma-globin and downstream of beta-globin are critical.
- These elements orchestrate the differential expression of globin genes during erythroid development.