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 β-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 β-globin gene expression. Thus, Mediator subunit Med1 plays a pivotal role in erythroid development and in β-globin gene activation.