title: 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.
authors.affiliation: Max-Planck-Institute of Immunobiology, 79108 Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Stumpf
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yue
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.forename: Hervé
authors.initials: H
authors.lastname: Luche
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.forename: Tilman
authors.initials: T
authors.lastname: Borggrefe
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology; D056913:Mediator Complex Subunit 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D014157:Transcription Factors; D055544:beta-Globins