MCB Accepts, published online ahead of print on 5 February 2007

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Mol. Cell. Biol. doi:10.1128/MCB.01658-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Erythroid Krüppel-like Factor Directly Activates the Basic Krüppel-like Factor Gene in Erythroid Cells

Alister P.W. Funnell, Christopher A. Maloney, Lucinda J. Thompson, Janelle Keys, Michael Tallack, Andrew C. Perkins, and Merlin Crossley^*

School of Molecular and Microbial Biosciences, G08, University of Sydney, NSW 2006, Australia.; Institute for Molecular Bioscience, University of Queensland, QLD, Australia

^* To whom correspondence should be addressed. Email: m.crossley{at}mmb.usyd.edu.au.

The Sp/Krüppel-like Factor (Sp/Klf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated Basic Krüppel-like Factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, Erythroid Krüppel-like Factor (Eklf/Klf1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf null murine embryos. We found that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, 1a, and an erythroid downstream promoter, 1b. Transcripts from both promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin-immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo.

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