Role of AP1/NFE2 binding sites in endogenous α-globin gene transcription
| العنوان: | Role of AP1/NFE2 binding sites in endogenous α-globin gene transcription |
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| المؤلفون: | Yasuhiro Okamoto, Mindy S. Randall, Paul A. Ney, Melanie R. Loyd |
| المصدر: | Blood. 102:4223-4228 |
| بيانات النشر: | American Society of Hematology, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Erythrocyte Indices, Ribosomal Proteins, Transcriptional Activation, Erythrocytes, Transcription, Genetic, Archaeal Proteins, Immunology, Cre recombinase, Biology, Biochemistry, Mice, Bone Marrow, Transcription (biology), hemic and lymphatic diseases, Animals, Gene, Transcription factor, Regulation of gene expression, Binding Sites, Cell Biology, Hematology, Embryo, Mammalian, Molecular biology, Globins, DNA-Binding Proteins, AP-1 transcription factor, Gene Expression Regulation, Liver, Regulatory sequence, NF-E2 Transcription Factor, p45 Subunit, Mutagenesis, Site-Directed, Erythroid-Specific DNA-Binding Factors, PAX6, Transcription Factors |
| الوصف: | High-level α-globin expression depends on cis-acting regulatory sequences located far upstream of the α-globin cluster. Sequences that contain the α-globin positive regulatory element (PRE) activate α-globin expression in transgenic mice. The α-globin PRE contains a pair of composite binding sites for the transcription factors activating protein 1 and nuclear factor erythroid 2 (AP1/NFE2). To determine the role of these binding sites in α-globin gene transcription, we mutated the AP1/NFE2 sites in the α-globin PRE in mice. We replaced the AP1/NFE2 sites with a neomycin resistance gene (neo) that is flanked by LoxP sites (floxed). Mice with this mutation exhibited increased embryonic death and α-thalassemia intermedia. Next, we removed the neo gene by Cre-mediated recombination, leaving a single LoxP site in place of the AP1/NFE2 sites. These mice were phenotypically normal. However, α-globin expression, measured by allele-specific RNA polymerase chain reaction (PCR), was decreased 25%. We examined the role of the hematopoietic-restricted transcription factor p45Nfe2 in activating expression through these sites and found that it is not required. Thus, we have demonstrated that AP1/NFE2 binding sites in the murine α-globin PRE contribute to long-range α-globin gene activation. The proteins that mediate this effect remain to be determined. (Blood. 2003;102:4223-4228) |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd550e2fec4deb6c1d9a730d2a84f496Test https://doi.org/10.1182/blood-2003-02-0574Test |
| رقم الانضمام: | edsair.doi.dedup.....bd550e2fec4deb6c1d9a730d2a84f496 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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