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  • Title: Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics.
    Author: Brand M, Ranish JA, Kummer NT, Hamilton J, Igarashi K, Francastel C, Chi TH, Crabtree GR, Aebersold R, Groudine M.
    Journal: Nat Struct Mol Biol; 2004 Jan; 11(1):73-80. PubMed ID: 14718926.
    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.
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