MCB Accepts, published online ahead of print on 15 October 2007

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siatecka, M. Articles by Bieker, J. J. Search for Related Content PubMed PubMed Citation Articles by Siatecka, M. Articles by Bieker, J. J.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.00589-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Sumoylation of EKLF Promotes Transcriptional Repression and Is Involved in Inhibition of Megakaryopoiesis

Miroslawa Siatecka, Li Xue, and James J. Bieker^*

The Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029

^* To whom correspondence should be addressed. Email: james.bieker{at}mssm.edu.

Erythroid Krüppel-like Factor (EKLF; KLF1) is a transcriptional regulator that plays a critical role within a specific subset of hematopoietic cells, particularly in the erythroid lineage and its immediate precursor, the megakaryocyte-erythroid progenitor (MEP). We find that EKLF is post-translationally modified by sumoylation at a single site near its amino terminus, and that PIAS1 plays a critical role in this process. Mutation of this site has little effect on EKLF's ability to function as a transcriptional activator; however, it has a dramatic effect on its repressive abilities. The mechanism of repression likely involves a novel SUMO-dependent EKLF interaction with the Mi2 component of the NuRD repression complex. Mutated EKLF is attenuated in its ability to repress megakaryocyte differentiation, implicating EKLF sumoylation status in differentiative decisions emanating from the MEP. These studies demonstrate a novel mechanism by which transcription factor sumoylation can alter protein-protein interactions and bipotential lineage decisions.

This article has been cited by other articles:

• Tallack, M. R., Keys, J. R., Humbert, P. O., Perkins, A. C. (2009). EKLF/KLF1 Controls Cell Cycle Entry via Direct Regulation of E2f2. J. Biol. Chem. 284: 20966-20974 [Abstract] [Full Text]  
• 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]  
• Sengupta, T., Chen, K., Milot, E., Bieker, J. J. (2008). Acetylation of EKLF Is Essential for Epigenetic Modification and Transcriptional Activation of the {beta}-Globin Locus. Mol. Cell. Biol. 28: 6160-6170 [Abstract] [Full Text]  
• Bouilloux, F., Juban, G., Cohet, N., Buet, D., Guyot, B., Vainchenker, W., Louache, F., Morle, F. (2008). EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation. Blood 112: 576-584 [Abstract] [Full Text]  
• Lohmann, F., Bieker, J. J. (2008). Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment. Development 135: 2071-2082 [Abstract] [Full Text]