Autonomous developmental control of human embryonic globin gene switching in transgenic mice.
The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (epsilon) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human epsilon-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human epsilon-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of epsilon gene expression in definitive erythroid cells suggests that the developmental regulation of the epsilon-globin gene depends only on the presence of the LCR and the epsilon-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of epsilon-globin gene developmental control distinguishes it from the competitive mechanism of regulation of gamma and beta-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.
Raich
N
N
Division of Medical Genetics, University of Washington, Seattle 98195.
Enver
T
T
Nakamoto
B
B
Josephson
B
B
Papayannopoulou
T
T
Stamatoyannopoulos
G
G
D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis; D005333:Fetus / Q000378:metabolism*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D012045:Regulatory Sequences, Nucleic Acid; D015017:Yolk Sac / Q000166:cytology
D006454:Hemoglobins; D005914:Globins