Regulation of human fetal hemoglobin gene expression.
ABSTRACT An understanding of the mechanism involved in the regulated expression of the human gamma and beta globin genes requires the detailed definition of the cis-acting DNA sequences and trans-acting protein factors responsible for their developmental stage specific expression. To determine the critical cis-acting elements, hybrid genes containing elements of the gamma and beta globin genes were transfected into K562 cells, a human erythroleukemia line. The regulated expression of the gamma and beta genes was also studied by transferring hybrid genes containing the gamma or beta promoters linked to the neomycin resistance gene (neoR) into erythroid (K562) cells and nonerythroid (Hela) cells. DNA sequences found to be important to the expression of the gamma gene were assayed for the presence of transacting factors by studying the binding of protein factors using the gel mobility shift assay. The results suggest that there are multiple cis-acting elements 5' and 3' to the gamma and beta genes, and perhaps within these genes contributing to their regulation. In addition, there are multiple trans-acting protein factors interacting with these regions which may determine their transcriptional regulation in erythroid cells.
- Cell 10/1986; 46(6):795-805. · 31.96 Impact Factor
- Methods in Enzymology 02/1980; 65(1):499-560. · 2.00 Impact Factor
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ABSTRACT: The enzymatic machinery that carries out RNA synthesis provides the cell with the means to adjust the patterns of transcription in response to environmental and developmental signals. In eukaryotes, this regulation is mediated in part by promoter-specific transcription factors, which are DNA-binding proteins with the ability to discriminate between distinctive DNA sequence elements found in the promoter regions of different genes. The presence of these factors bound to DNA enables other components of the transcriptional machinery, including the RNA polymerase, to initiate transcription with selectivity and accuracy.Nature 01/1985; 316(6031):774-8. · 38.60 Impact Factor