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PMID: 9223298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 15 ·1997-07-22 ·Pages 7976-81

McDevitt MA, Fujiwara Y, Shivdasani RA, Orkin SH

Abstract

The transcription factor GATA-1, which is expressed in several hematopoietic lineages and multipotential progenitors, is required for the development of red blood cells and platelets. To identify control elements of the mouse GATA-1 gene, we analyzed DNase I hypersensitivity of the locus in erythroid chromatin and the expression of GATA-1/Escherichia coli beta-galactosidase (lacZ) transgenes in mice. Transgenes with 2.7 kb of promoter sequences are expressed infrequently and only within adult (definitive) erythroid cells. We show that inclusion of an upstream hypersensitive site (HS I) markedly enhances the frequency of expressing transgenic lines and activates expression in primitive erythroid cells. This pattern recapitulates the proper pattern of GATA-1 expression during development. By breeding a GATA-1/lacZ transgene into a GATA-1(-) background, we also have shown that the activation or maintenance of GATA-1 expression does not require the presence of GATA-1 itself, thereby excluding simple models of positive autoregulation. The transgene cassette reported here should be useful in directing expression of foreign sequences at the onset of hematopoiesis in the embryo and may assist in the identification of upstream regulators of the GATA-1 gene.

MeSH Terms
3T3 Cells Aging/genetics Animals DNA-Binding Proteins/genetics Deoxyribonuclease I/metabolism Eosinophils/metabolism Erythroid-Specific DNA-Binding Factors Erythropoiesis/genetics GATA1 Transcription Factor Hematopoietic Stem Cells/metabolism Lac Operon Mast Cells/metabolism Megakaryocytes/metabolism Mice Mice, Inbred C57BL Mice, Transgenic/genetics,growth & development Promoter Regions, Genetic Transcription Factors/genetics Transgenes
Chemicals
DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gata1 protein, mouse Transcription Factors Deoxyribonuclease I
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McDevitt M A
Department of Medicine, Harvard Medical School, Boston MA 02115, USA.
Fujiwara Y
Shivdasani R A
Orkin S H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.15.7976
Published
1997-07-22
Pages
7976-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21540
Subset
IM
Grants
NHLBI NIH HHS · T32 HL007623 · United States
NHLBI NIH HHS · T32HL07623 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.15.7976 PMC Full Text View journal details
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