Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics

Marjorie Brand, Jeffrey A. Ranish, Nicolas T. Kummer, Joan Hamilton, Kazuhiko Igarashi, Claire Francastel, Tian H. Chi, Gerald R. Crabtree, Ruedi Aebersold, Mark Groudine

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183 Citations (Scopus)

Abstract

During erythroid differentiation, β-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 β-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 corepressors and co-activators. Thus, our results suggest that in addition to its role as a cis-acting activator of β-globin gene expression in differentiated erythroid cells, the LCR also promotes an active repression of β-globin transcription in committed cells before terminal differentiation.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalNature Structural and Molecular Biology
Volume11
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Brand, M., Ranish, J. A., Kummer, N. T., Hamilton, J., Igarashi, K., Francastel, C., Chi, T. H., Crabtree, G. R., Aebersold, R., & Groudine, M. (2004). Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics. Nature Structural and Molecular Biology, 11(1), 73-80. https://doi.org/10.1038/nsmb713