Unanticipated Repression Function Linked to Erythroid Krüppel-Like Factor

Abstract

The erythroid cell-specific transcription factor erythroid Krüppel-like factor (EKLF) is an important activator of β-globin gene expression. It achieves this by binding to the CACCC element at the β-globin promoter via its zinc finger domain. The coactivators CBP and P300 interact with, acetylate, and enhance its activity, helping to explain its role as a transcription activator. Here we show that EKLF can also interact with the corepressors mSin3A and HDAC1 (histone deacetylase 1) through its zinc finger domain. When linked to a GAL4 DNA binding domain, full-length EKLF or its zinc finger domain alone can repress transcription in vivo. This repressive activity can be relieved by the HDAC inhibitor trichostatin A. Although recruitment of EKLF to a promoter is required to show repression, its zinc finger domain cannot bind directly to DNA and repress transcription simultaneously. In addition, the target promoter configuration is important for enabling EKLF to exhibit any repressive activity. These results suggest that EKLF may function in vivo as a transcription repressor and play a previously unsuspected additional role in regulating erythroid gene expression and differentiation.

ACKNOWLEDGMENTS

We thank J. Licht, M. Crossley, R. Eisenman, C. Hassig, and S. Schreiber for plasmids.

This work was supported by PHS grant DK46865 to J.J.B., who is a Scholar of the Leukemia Society of America.