Specific erythroid-lineage defect in mice conditionally deficient for Mediator subunit Med1.

ABSTRACT: The Mediator complex forms the bridge between transcriptional activators and the RNA polymerase II. Med1 (also known as PBP or TRAP220) is a key component of Mediator that interacts with nuclear hormone receptors and GATA transcription factors. Here, we show dynamic recruitment of GATA-1, TFIIB, Mediator, and RNA polymerase II to the ?-globin locus in induced mouse erythroid leukemia cells and in an erythropoietin-inducible hematopoietic progenitor cell line. Using Med1 conditional knockout mice, we demonstrate a specific block in erythroid development but not in myeloid or lymphoid development, highlighted by the complete absence of ?-globin gene expression. Thus, Mediator subunit Med1 plays a pivotal role in erythroid development and in ?-globin gene activation.

SUBMITTER: Stumpf M 

PROVIDER: S-EPMC3003004 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature