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PMID:17132730

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Citation

Stumpf, M, Waskow, C, Krötschel, M, van Essen, D, Rodriguez, P, Zhang, X, Guyot, B, Roeder, RG and Borggrefe, T (2006) The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc. Natl. Acad. Sci. U.S.A. 103:18504-9

Abstract

The Mediator complex forms the bridge between transcriptional activators and RNA polymerase II. Mediator subunit Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors. Med1 deficiency causes lethality at embryonic day 11.5 because of defects in heart and placenta development. Here we show that Med1-deficient 10.5 days postcoitum embryos are anemic but have normal numbers of hematopoietic progenitor cells. Med1-deficient progenitor cells have a defect in forming erythroid burst-forming units (BFU-E) and colony-forming units (CFU-E), but not in forming myeloid colonies. At the molecular level, we demonstrate that Med1 interacts physically with the erythroid master regulator GATA-1. In transcription assays, Med1 deficiency leads to a defect in GATA-1-mediated transactivation. In chromatin immunoprecipitation experiments, we find Mediator components at GATA-1-occupied enhancer sites. Thus, we conclude that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development.

Links

PubMed PMC1693692 Online version:10.1073/pnas.0604494103

Keywords

Animals; Cell Line; Embryonic Stem Cells/metabolism; Endodeoxyribonucleases/deficiency; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/physiology; Erythroid Precursor Cells/cytology; Erythropoiesis/physiology; GATA1 Transcription Factor/physiology; Mediator Complex Subunit 1; Mice; Mice, Knockout; Protein Subunits/physiology; Proto-Oncogene Proteins c-kit/metabolism; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GATA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15648

F

Seeded From UniProt

complete

HUMAN:MED1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15976

F

Seeded From UniProt

complete

MOUSE:MED1

acts_upstream_of_or_within

GO:0048821: erythrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1861125

P

Seeded From UniProt

complete


See also

References

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