Molecular and Cellular Biology, May 2001, p. 3118-3125, Vol. 21, No. 9
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.9.3118-3125.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029
Received 22 August 2000/Returned for modification 25 September 2000/Accepted 14 February 2001
The erythroid cell-specific transcription factor erythroid
Krüppel-like factor (EKLF) is an important activator of
-globin gene expression. It achieves this by binding to the CACCC
element at the
-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.
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