| Literature DB >> 14718926 |
Marjorie Brand1, Jeffrey A Ranish, Nicolas T Kummer, Joan Hamilton, Kazuhiko Igarashi, Claire Francastel, Tian H Chi, Gerald R Crabtree, Ruedi Aebersold, Mark Groudine.
Abstract
During erythroid differentiation, beta-globin gene expression is regulated by the locus control region (LCR). The transcription factor NF-E2p18/MafK binds within this region and is essential for beta-globin expression in murine erythroleukemia (MEL) cells. Here we use the isotope-coded affinity tag (ICAT) technique of quantitative mass spectrometry to compare proteins interacting with NF-E2p18/MafK during differentiation. Our results define MafK as a 'dual-function' molecule that shifts from a repressive to an activating mode during erythroid differentiation. The exchange of MafK dimerization partner from Bach1 to NF-E2p45 is a key step in the switch from the repressed to the active state. This shift is associated with changes in the interaction of MafK with co-repressors and co-activators. Thus, our results suggest that in addition to its role as a cis-acting activator of beta-globin gene expression in differentiated erythroid cells, the LCR also promotes an active repression of beta-globin transcription in committed cells before terminal differentiation.Entities:
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Year: 2003 PMID: 14718926 DOI: 10.1038/nsmb713
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN: 1545-9985 Impact factor: 15.369