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Molecular and Cellular Biology, December 2004, p. 10416-10424, Vol. 24, No. 23
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.23.10416-10424.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Stage-Specific Repression by the EKLF Transcriptional Activator

Xiaoyong Chen and James J. Bieker*

Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, New York

Received 26 July 2004/ Returned for modification 2 September 2004/ Accepted 9 September 2004

Dynamic changes in transcription factor function can be mediated by switching its interaction with coactivators and corepressors. Erythroid Krüppel-like factor (EKLF) is an erythroid cell-specific transcription factor that plays a critical role in ß-globin gene activation via its interactions with CBP/p300 and SWI/SNF proteins. Unexpectedly, it also interacts with Sin3A and histone deacetylase 1 (HDAC1) corepressors via its zinc finger domain. We now find that selected point mutants can uncouple activation and repression and that an intact finger structure is not required for interactions with Sin3A/HDAC1 or for transrepression. Most intriguingly, EKLF repression exhibits stage specificity, with reversible EKLF-Sin3A interactions playing a key role in this process. Finally, we have located a key lysine residue that is both a substrate for CBP acetylation and required for Sin3A interaction. These data suggest a model whereby the stage of the erythroid cell alters the acetylation status of EKLF and plays a critical role in directing its coactivator-corepressor interactions and downstream transcriptional effects.

* Corresponding author. Mailing address: Mount Sinai School of Medicine, Brookdale Department of Molecular, Cell and Developmental Biology, Box 1020, One Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-4143. Fax: (212) 860-9279. E-mail: james.bieker{at}mssm.edu.

Molecular and Cellular Biology, December 2004, p. 10416-10424, Vol. 24, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.23.10416-10424.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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