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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.

Unanticipated Repression Function Linked to Erythroid Krüppel-Like Factor

Xiaoyong Chen* and James J. Bieker

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 beta -globin gene expression. It achieves this by binding to the CACCC element at the beta -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.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029. Phone: (212) 241-4143. Fax: (212) 860-9272. E-mail: chenx02{at}doc.mssm.edu.

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.


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