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Article Dans Une Revue Blood Année : 2008

EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation.

Résumé

Previous observations suggested that functional antagonism between FLI-1 and EKLF might be involved in the commitment toward erythrocytic or megakaryocytic differentiation. We show here using inducible shRNA expression, that EKLF knockdown in MEL cells decreases erythrocytic and increases megakaryocytic as well as fli-1 gene expression. Chromatin immunoprecipitation analyses revealed that the increase in megakaryocytic gene expression is associated with a marked increase in RNA pol II and FLI-1 occupancy at their promoters albeit FLI-1 protein levels are only minimally affected. Similarly, we show that human CD34(+) progenitors infected with shRNA lentivirus allowing EKLF knockdown generate an increased number of differentiated megakaryocytic cells associated with increased levels of megakaryocytic and fli-1 gene transcripts. Single cell progeny analysis of a cell population enriched in bipotent progenitors revealed that EKLF knockdown increases the number of megakaryocytic at the expense of erythrocytic colonies. Taken together, these data indicate that EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation and suggest that this might be at least partially mediated by the inhibition of FLI-1 recruitment to megakaryocytic and fli-1 gene promoters.

Dates et versions

hal-00294040 , version 1 (08-07-2008)

Identifiants

Citer

Fabrice Bouilloux, Gaetan Juban, Nathalie Cohet, Dorothee Buet, Boris Guyot, et al.. EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation.. Blood, 2008, epub ahead of print. ⟨10.1182/blood-2007-07-098996⟩. ⟨hal-00294040⟩
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