Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 50, Pages 21541-21546Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1005794107
Keywords
blood; hematopoiesis; erythropoiesis; transcriptional regulation; globin
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Funding
- Deutsche Forschungsgemeinschaft [BOR-1639/4-1]
- Emmy-Noether Fellowship [BO1639/3]
- Collaborative Research Center [SFB592/C3]
- Max Planck Society
- National Institutes of Health [GM23750, DK083163]
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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 beta-globin locus in induced mouse erythoid 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 beta-globin gene expression. Thus, Mediator subunit Med1 plays a pivotal role in erythroid development and in beta-globin gene activation.
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