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 linke...
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| Published in: | Science (American Association for the Advancement of Science) Vol. 250; no. 4984; pp. 1147 - 1149 |
|---|---|
| Main Authors: | , , , , , |
| 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 |
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| Abstract | 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. |
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| AbstractList | Recent research is presented on the mechanisms by which expression of the beta-like globin genes are developmentally regulated. At least two distinct mechanisms were found to function in human hemoglobin switching. 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. The mechanisms by which expression of the β-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (ε) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human ε-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 ε-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 ε gene expression in definitive erythroid cells suggests that the developmental regulation of the ε-globin gene depends only on the presence of the LCR and the ε-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of ε-globin gene developmental control distinguishes it from the competitive mechanism of regulation of γ and β-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching. |
| Audience | Academic |
| Author | NAKAMOTO, B PAPAYANNOPOULOU, T STAMATOYANNOPOULOS, G RAICH, N ENVER, T JOSEPHSON, B |
| Author_xml | – sequence: 1 givenname: N surname: RAICH fullname: RAICH, N organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States – sequence: 2 givenname: T surname: ENVER fullname: ENVER, T organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States – sequence: 3 givenname: B surname: NAKAMOTO fullname: NAKAMOTO, B organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States – sequence: 4 givenname: B surname: JOSEPHSON fullname: JOSEPHSON, B organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States – sequence: 5 givenname: T surname: PAPAYANNOPOULOU fullname: PAPAYANNOPOULOU, T organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States – sequence: 6 givenname: G surname: STAMATOYANNOPOULOS fullname: STAMATOYANNOPOULOS, G organization: Univ. Washington, div. medical genetics, Seattle WA 98195, United States |
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| ContentType | Journal Article |
| Copyright | 1991 INIST-CNRS COPYRIGHT 1990 American Association for the Advancement of Science COPYRIGHT 1990 American Association for the Advancement of Science Copyright American Association for the Advancement of Science Nov 23, 1990 |
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| Issue | 4984 |
| Keywords | Globin Human Embryonic development Regulation(control) Erythroid cell Gene Transgenic animal Gene expression Immunofluorescence Switching Fetal hemoglobin |
| Language | English |
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| References | (e_1_2_1_9_1) 1989; 86 (e_1_2_1_18_1) 1989; 86 (e_1_2_1_15_1) 1984; 259 (e_1_2_1_13_1) 1987; 51 (e_1_2_1_20_1) 1985; 82 (e_1_2_1_12_1) 1987; 52 (e_1_2_1_6_1) 1988; 55 (e_1_2_1_4_1) 1989; 86 (e_1_2_1_11_1) 1989; 86 (e_1_2_1_21_1) 1989; 56 (e_1_2_1_14_1) 1989; 3 (e_1_2_1_16_1) 1989; 180 (e_1_2_1_3_1) 1990; 4 (e_1_2_1_17_1) 1988; 85 (e_1_2_1_1_1) 1980; 21 (e_1_2_1_8_1) 1990; 344 (e_1_2_1_10_1) 1986; 83 (e_1_2_1_5_1) 1986; 319 (e_1_2_1_2_1) 1986; 46 (e_1_2_1_7_1) 1985; 50 (e_1_2_1_19_1) 1989; 338 |
| References_xml | – volume: 86 start-page: 5306 year: 1989 ident: e_1_2_1_4_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 51 start-page: 975 year: 1987 ident: e_1_2_1_13_1 publication-title: CELL doi: 10.1016/0092-8674(87)90584-8 – volume: 21 start-page: 621 year: 1980 ident: e_1_2_1_1_1 publication-title: CELL doi: 10.1016/0092-8674(80)90425-0 – volume: 180 start-page: 303 year: 1989 ident: e_1_2_1_16_1 publication-title: ANALYTICAL BIOCHEMISTRY doi: 10.1016/0003-2697(89)90435-1 – volume: 52 start-page: 875 year: 1987 ident: e_1_2_1_12_1 publication-title: COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY doi: 10.1101/SQB.1987.052.01.096 – volume: 86 start-page: 5439 year: 1989 ident: e_1_2_1_11_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 83 start-page: 1359 year: 1986 ident: e_1_2_1_10_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 82 start-page: 6384 year: 1985 ident: e_1_2_1_20_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 319 start-page: 685 year: 1986 ident: e_1_2_1_5_1 publication-title: NATURE doi: 10.1038/319685a0 – volume: 86 start-page: 7033 year: 1989 ident: e_1_2_1_9_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 3 start-page: 1572 year: 1989 ident: e_1_2_1_14_1 publication-title: GENES & DEVELOPMENT doi: 10.1101/gad.3.10.1572 – volume: 259 start-page: 3739 year: 1984 ident: e_1_2_1_15_1 publication-title: JOURNAL OF BIOLOGICAL CHEMISTRY doi: 10.1016/S0021-9258(17)43157-7 – volume: 85 start-page: 2548 year: 1988 ident: e_1_2_1_17_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 50 start-page: 361 year: 1985 ident: e_1_2_1_7_1 publication-title: Cold Spring Harbor Symposia on Quantitative Biology doi: 10.1101/SQB.1985.050.01.046 – volume: 46 start-page: 591 year: 1986 ident: e_1_2_1_2_1 publication-title: CELL doi: 10.1016/0092-8674(86)90885-8 – volume: 344 start-page: 309 year: 1990 ident: e_1_2_1_8_1 publication-title: NATURE doi: 10.1038/344309a0 – volume: 338 start-page: 352 year: 1989 ident: e_1_2_1_19_1 publication-title: NATURE doi: 10.1038/338352a0 – volume: 86 start-page: 37 year: 1989 ident: e_1_2_1_18_1 publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA – volume: 4 start-page: 380 year: 1990 ident: e_1_2_1_3_1 publication-title: GENES & DEVELOPMENT doi: 10.1101/gad.4.3.380 – volume: 56 start-page: 969 year: 1989 ident: e_1_2_1_21_1 publication-title: CELL doi: 10.1016/0092-8674(89)90630-2 – volume: 55 start-page: 17 year: 1988 ident: e_1_2_1_6_1 publication-title: CELL doi: 10.1016/0092-8674(88)90005-0 |
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| Snippet | The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human... The mechanisms by which expression of the β-like globin genes are developmentally regulated are under intense investigation. The temporal control of human... Recent research is presented on the mechanisms by which expression of the beta-like globin genes are developmentally regulated. At least two distinct... The mechanisms by which expression of the beta -like globin genes are developmentally regulated are under intense investigation. The temporal control of human... The mechanisms by which expression of the {beta}-like globin genes are developmentally regulated are under intense investigation. The temporal control of human... |
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| SubjectTerms | 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 |
| Title | Autonomous developmental control of human embryonic globin gene switching in transgenic mice |
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