Lineage-specific combinatorial action of enhancers regulates mouse erythroid Gata1 expression.
Blood
; 115(17): 3463-71, 2010 Apr 29.
Article
en En
| MEDLINE
| ID: mdl-20154211
ABSTRACT
Precise spatiotemporal control of Gata1 expression is required in both early hematopoietic progenitors to determine erythroid/megakaryocyte versus granulocyte/monocyte lineage output and in the subsequent differentiation of erythroid cells and megakaryocytes. An enhancer element upstream of the mouse Gata1 IE (1st exon erythroid) promoter, mHS-3.5, can direct both erythroid and megakaryocytic expression. However, loss of this element ablates only megakaryocytes, implying that an additional element has erythroid specificity. Here, we identify a double DNaseI hypersensitive site, mHS-25/6, as having erythroid but not megakaryocytic activity in primary cells. It binds an activating transcription factor complex in erythroid cells where it also makes physical contact with the Gata1 promoter. Deletion of mHS-25/6 or mHS-3.5 in embryonic stem cells has only a modest effect on in vitro erythroid differentiation, whereas loss of both elements ablates both primitive and definitive erythropoiesis with an almost complete loss of Gata1 expression. Surprisingly, Gata2 expression was also concomitantly low, suggesting a more complex interaction between these 2 factors than currently envisaged. Thus, whereas mHS-3.5 alone is sufficient for megakaryocytic development, mHS-3.5 and mHS-25/6 collectively regulate erythroid Gata1 expression, demonstrating lineage-specific differences in Gata1 cis-element use important for development of these 2 cell types.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Megacariocitos
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Regulación de la Expresión Génica
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Elementos de Facilitación Genéticos
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Células Eritroides
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Eritropoyesis
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Factor de Transcripción GATA1
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Células Madre Embrionarias
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Blood
Año:
2010
Tipo del documento:
Article