Document Detail

Impaired in vitro erythropoiesis following deletion of the Scl (Tal1) +40 enhancer is largely compensated for in vivo despite a significant reduction in expression.
MedLine Citation:
PMID:  23319051     Owner:  NLM     Status:  MEDLINE    
The Scl (Tal1) gene encodes a helix-loop-helix transcription factor essential for hematopoietic 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 germ line. Scl(Δ40/Δ40) mice were viable with reduced numbers of erythroid CFU in both bone marrow and spleen yet displayed a normal response to stress hematopoiesis. Analysis of Scl(Δ40/Δ40) embryonic stem (ES) cells revealed impaired erythroid differentiation, which was accompanied by a failure to upregulate Scl when erythropoiesis was initiated. Map17 expression was also reduced in hematopoietic 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 cell-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.
Rita Ferreira; Dominik Spensberger; Yvonne Silber; Andrew Dimond; Juan Li; Anthony R Green; Berthold Göttgens
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  Molecular and cellular biology     Volume:  33     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-07-05     Revised Date:  2014-05-13    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1254-66     Citation Subset:  IM    
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / deficiency,  genetics*,  metabolism*
Bone Marrow / metabolism
Cell Differentiation / genetics
DNA-Binding Proteins / genetics,  metabolism
Embryonic Stem Cells / metabolism
Enhancer Elements, Genetic / genetics*
Erythroid Cells / metabolism
Erythropoiesis / genetics*
Hematopoiesis / genetics
Membrane Proteins / genetics,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Proteins / deficiency,  genetics*,  metabolism*
Spleen / metabolism
Grant Support
079249//Wellcome Trust; 100140//Wellcome Trust; //Biotechnology and Biological Sciences Research Council; //Cancer Research UK; //Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA-Binding Proteins; 0/Membrane Proteins; 0/Pdzk1ip1 protein, mouse; 0/Proto-Oncogene Proteins; 0/Tal1 protein, mouse

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