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

Marjorie Brand1, Jeffrey A Ranish, Nicolas T Kummer

  • 1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Nature Structural & Molecular Biology
|January 14, 2004
PubMed
Summary

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The transcription factor MafK changes its role from repressing to activating beta-globin gene expression during erythroid differentiation, by switching partners. This reveals a dual function for MafK and LCR regulation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Proteomics

Background:

  • Beta-globin gene expression is crucial for erythroid differentiation.
  • The locus control region (LCR) regulates beta-globin expression.
  • NF-E2p18/MafK is a key transcription factor binding to the LCR.

Purpose of the Study:

  • To investigate the dynamic changes in protein interactions with NF-E2p18/MafK during erythroid differentiation.
  • To understand the regulatory mechanisms of beta-globin gene expression controlled by the LCR.

Main Methods:

  • Quantitative mass spectrometry using the isotope-coded affinity tag (ICAT) technique.
  • Comparison of protein interactions with NF-E2p18/MafK in murine erythroleukemia (MEL) cells during differentiation.

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Main Results:

  • MafK exhibits a dual function, transitioning from a repressive to an activating role during differentiation.
  • A key switch involves MafK exchanging its dimerization partner from Bach1 to NF-E2p45.
  • These partner exchanges correlate with altered interactions with co-repressors and co-activators.

Conclusions:

  • MafK acts as a dynamic regulator, shifting its function based on differentiation stage.
  • The LCR not only activates but also actively represses beta-globin transcription before terminal differentiation.
  • Understanding these regulatory shifts provides insights into globin gene control.