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Molecular and Cellular Biology, October 2008, p. 6160-6170, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00919-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Acetylation of EKLF Is Essential for Epigenetic Modification and Transcriptional Activation of the β-Globin Locus{triangledown}

Tanushri Sengupta,1 Ken Chen,1 Eric Milot,2 and James J. Bieker1*

Mount Sinai School of Medicine, New York, New York,1 Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec, Canada2

Received 9 June 2008/ Returned for modification 10 July 2008/ Accepted 6 August 2008

Posttranslational modifications of transcription factors provide alternate protein interaction platforms that lead to varied downstream effects. We have investigated how the acetylation of EKLF plays a role in its ability to alter the β-like globin locus chromatin structure and activate transcription of the adult β-globin gene. By establishing an EKLF-null erythroid line whose closed β-locus chromatin structure and silent β-globin gene status can be rescued by retroviral infection of EKLF, we demonstrate the importance of EKLF acetylation at lysine 288 in the recruitment of CBP to the locus, modification of histone H3, occupancy by EKLF, opening of the chromatin structure, and transcription of adult β-globin. We also find that EKLF helps to coordinate this process by the specific association of its zinc finger domain with the histone H3 amino terminus. Although EKLF interacts equally well with H3.1 and H3.3, we find that only H3.3 is enriched at the adult β-globin promoter. These data emphasize the critical nature of lysine acetylation in transcription factor activity and enable us to propose a model of how modified EKLF integrates coactivators, chromatin remodelers, and nucleosomal components to alter epigenetic chromatin structure and stimulate transcription.

* Corresponding author. Mailing address: Mount Sinai School of Medicine, Department of Developmental and Regenerative 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

{triangledown} Published ahead of print on 18 August 2008.

Molecular and Cellular Biology, October 2008, p. 6160-6170, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00919-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sengupta, T., Cohet, N., Morle, F., Bieker, J. J. (2009). Distinct modes of gene regulation by a cell-specific transcriptional activator. Proc. Natl. Acad. Sci. USA 106: 4213-4218 [Abstract] [Full Text]  


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