| Impaired In Vitro Erythropoiesis Following Deletion of the Scl/Tal1 +40 Enhancer Is Largely Compensated In Vivo Despite Significant Reduction in Expression. | |
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MedLine Citation:
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PMID: 23319051 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The Scl/Tal1 gene encodes a helix-loop-helix transcription factor essential for haematopoietic stem cell and erythroid development. The Scl+40 enhancer is situated downstream of Map17, the 3' flanking gene of Scl, and is active in transgenic mice during primitive and definitive erythropoiesis. To analyze the in vivo function of the Scl+40 enhancer within the Scl/Map17 transcriptional domain, we deleted this element in the germline. Scl(Δ40/Δ40) mice were viable with reduced numbers of CFU-e in both bone marrow and spleen, yet displayed a normal response to stress haematopoiesis. Analysis of Scl(Δ40/Δ40) embryonic stem (ES) cells revealed impaired erythroid differentiation, which was accompanied by a failure to upregulate Scl when erythropoiesis is initiated. Map17 expression was also reduced in haematopoietic tissues and differentiating ES cells, and the Scl +40 element was able to enhance activity of the Map17 promoter. However, only Scl but not Map17 could rescue the Scl(Δ40/Δ40) ES phenotype. Together, these data demonstrate that the Scl+40 enhancer is an erythroid-specific enhancer that regulates the expression of both Scl and Map17. Moreover, deletion of the +40 enhancer causes a novel erythroid phenotype, which can be rescued by ectopic expression of Scl but not Map17. |
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Authors:
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Rita Ferreira; Dominik Spensberger; Yvonne Silber; Andrew Dimond; Juan Li; Anthony R Green; Berthold Göttgens |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-14 |
Journal Detail:
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Title: Molecular and cellular biology Volume: - ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Haematology, Cambridge Institute for Medical Research & Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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