scholarly journals The chicken beta globin gene region. Delineation of transcription units and developmental regulation of interspersed DNA repeats.

1982 ◽  
Vol 257 (18) ◽  
pp. 11015-11023 ◽  
Author(s):  
B Villeponteau ◽  
G M Landes ◽  
M J Pankratz ◽  
H G Martinson
Keyword(s):  
Developmental Regulation ◽  
Globin Gene ◽  
Gene Region ◽  
Dna Repeats ◽  
Beta Globin ◽  
Beta Globin Gene

scholarly journals The gamma-delta-beta-globin gene region in G gamma-beta +-hereditary persistence of fetal hemoglobin

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 828-831
Author(s):  
JF Balsley ◽  
E Rappaport ◽  
E Schwartz ◽  
S Surrey
Keyword(s):  
Globin Gene ◽  
Blot Hybridization ◽  
Fetal Hemoglobin ◽  
Restriction Enzymes ◽  
Restriction Endonuclease Analysis ◽  
Gene Region ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Hereditary Persistence

We report restriction endonuclease analysis of the gamma-delta-beta- globin gene region in a mother and child heterozygous for G gamma-beta +-hereditary persistence of fetal hemoglobin (HPFH). The affected chromosome in these persons directs the production of G gamma-chains and beta-chains but not A gamma-chains. DNA was digested with several restriction enzymes and was examined for gamma, delta, beta sequences by blot hybridization. Only normal digestion fragments were present. By sensitive methods, we were unable to detect a deletion in the entire gamma-delta-beta-globin gene region of the affected chromosome, indicating that in this family, G gamma-beta +-HPFH is not due to a large deletion.

scholarly journals Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes.

1990 ◽  
Vol 10 (3) ◽  
pp. 1116-1125 ◽  
Author(s):  
C Perez-Stable ◽  
F Costantini
Keyword(s):  
Blood Cells ◽  
Developmental Regulation ◽  
Globin Gene ◽  
Upstream Region ◽  
Globin Genes ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Cis Acting ◽  
Beta Globin Gene ◽  
Gamma Globin

The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patterns of expression are located 5' to the G gamma-globin gene and 3' to the beta-globin gene. To further define the locations and functional roles of these elements, we examined the effects of 5' truncations on the expression of the G gamma-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene. We found that sequences between -201 and -136 are essential for expression of the G gamma-globin gene, whereas those upstream of -201 have little effect on the level or tissue or stage specificity of G gamma-globin expression. The G gamma-globin upstream sequences from -201 to -136 were, furthermore, capable of activating a linked beta-globin gene in embryonic blood cells; however, a G gamma-globin fragment from -383 to -206 was similarly active in this assay, and the complete fragment from -383 to -136 was considerably more active than either of the smaller fragments, suggesting the presence of multiple cis-acting elements for embryonic blood cells. Our data also suggested the possibility of a negative regulatory element between -201 and -136. These results are discussed in relation to several DNA elements in the G gamma-globin upstream region, which have been shown to bind nuclear factors in erythroid cells. Finally, we observed that removal of the beta-globin 3'-flanking sequences, including the 3' enhancer, from the G gamma-globin upstream-beta-globin hybrid gene resulted in a 25-fold reduction in expression in embryonic blood cells. This suggests that the beta-globin 3' enhancer is potentially active at the embryonic stage and thus cannot be solely responsible for the fetal or adult specificity of the beta-globin gene.

Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes

1990 ◽  
Vol 10 (3) ◽  
pp. 1116-1125
Author(s):  
C Perez-Stable ◽  
F Costantini
Keyword(s):  
Blood Cells ◽  
Developmental Regulation ◽  
Globin Gene ◽  
Upstream Region ◽  
Globin Genes ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Cis Acting ◽  
Beta Globin Gene ◽  
Gamma Globin

The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patterns of expression are located 5' to the G gamma-globin gene and 3' to the beta-globin gene. To further define the locations and functional roles of these elements, we examined the effects of 5' truncations on the expression of the G gamma-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene. We found that sequences between -201 and -136 are essential for expression of the G gamma-globin gene, whereas those upstream of -201 have little effect on the level or tissue or stage specificity of G gamma-globin expression. The G gamma-globin upstream sequences from -201 to -136 were, furthermore, capable of activating a linked beta-globin gene in embryonic blood cells; however, a G gamma-globin fragment from -383 to -206 was similarly active in this assay, and the complete fragment from -383 to -136 was considerably more active than either of the smaller fragments, suggesting the presence of multiple cis-acting elements for embryonic blood cells. Our data also suggested the possibility of a negative regulatory element between -201 and -136. These results are discussed in relation to several DNA elements in the G gamma-globin upstream region, which have been shown to bind nuclear factors in erythroid cells. Finally, we observed that removal of the beta-globin 3'-flanking sequences, including the 3' enhancer, from the G gamma-globin upstream-beta-globin hybrid gene resulted in a 25-fold reduction in expression in embryonic blood cells. This suggests that the beta-globin 3' enhancer is potentially active at the embryonic stage and thus cannot be solely responsible for the fetal or adult specificity of the beta-globin gene.

scholarly journals Human gamma- to beta-globin gene switching using a mini construct in transgenic mice.

1992 ◽  
Vol 12 (4) ◽  
pp. 1561-1567 ◽  
Author(s):  
J A Lloyd ◽  
J M Krakowsky ◽  
S C Crable ◽  
J B Lingrel
Keyword(s):  
Transgenic Mice ◽  
Developmental Regulation ◽  
Globin Gene ◽  
Globin Genes ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Gamma Globin ◽  
High Level ◽  
Gene Switching ◽  
Globin Gene Expression

The developmental regulation of the human globin genes involves a key switch from fetal (gamma-) to adult (beta-) globin gene expression. It is possible to study the mechanism of this switch by expressing the human globin genes in transgenic mice. Previous work has shown that high-level expression of the human globin genes in transgenic mice requires the presence of the locus control region (LCR) upstream of the genes in the beta-globin locus. High-level, correct developmental regulation of beta-globin gene expression in transgenic mice has previously been accomplished only in 30- to 40-kb genomic constructs containing the LCR and multiple genes from the locus. This suggests that either competition for LCR sequences by other globin genes or the presence of intergenic sequences from the beta-globin locus is required to silence the beta-globin gene in embryonic life. The results presented here clearly show that the presence of the gamma-globin gene (3.3 kb) alone is sufficient to down-regulate the beta-globin gene in embryonic transgenic mice made with an LCR-gamma-beta-globin mini construct. The results also show that the gamma-globin gene is down-regulated in adult mice from most transgenic lines made with LCR-gamma-globin constructs not including the beta-globin gene, i.e., that the gamma-globin gene can be autonomously regulated. Evidence presented here suggests that a region 3' of the gamma-globin gene may be important for down-regulation in the adult. The 5'HS2 gamma en beta construct described is a suitable model for further study of the mechanism of human gamma- to beta-globin gene switching in transgenic mice.

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