Autonomous developmental control of human embryonic globin gene switching in transgenic mice

• Published in: Science (American Association for the Advancement of Science) Vol. 250; no. 4984; pp. 1147 - 1149
• Main Authors: RAICH, N, ENVER, T, NAKAMOTO, B, JOSEPHSON, B, PAPAYANNOPOULOU, T, STAMATOYANNOPOULOS, G
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 23-11-1990; The American Association for the Advancement of Science
• Subjects: 550200 - Biochemistry; ANIMALS; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; Bone Marrow - embryology; Bone Marrow Cells; Developmental genetics; EMBRYOS; ERYTHROCYTES; Erythroid Precursor Cells - metabolism; Erythropoiesis; Expression; Fetus - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; GENE REGULATION; GENES; GENETIC ENGINEERING; Genetically modified mice; Genetics; Globin genes; GLOBINS; Globins - genetics; Hemoglobins - biosynthesis; Humans; Liver - cytology; Liver - embryology; MAMMALS; MAN; MATERIALS; MICE; Mice, Transgenic; Molecular and cellular biology; Molecular genetics; ONTOGENESIS; ORGANIC COMPOUNDS; PRIMATES; PROTEINS; Regulatory Sequences, Nucleic Acid; RODENTS; VERTEBRATES; Yolk Sac - cytology; Globin; Human; Embryonic development; Regulation(control); Erythroid cell; Gene; Transgenic animal; Gene expression; Immunofluorescence; Switching; Fetal hemoglobin
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2251502

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.