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Molecular and Cellular Biology, December 2007, p. 8547-8560, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00589-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sumoylation of EKLF Promotes Transcriptional Repression and Is Involved in Inhibition of Megakaryopoiesis{triangledown} ,{dagger}

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

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

Received 3 April 2007/ Returned for modification 11 May 2007/ Accepted 30 September 2007

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 posttranslationally 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 small ubiquitin-related modifier (SUMO)-dependent EKLF interaction with the Mi-2ß 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.

* Corresponding author. Mailing address: Mount Sinai School of Medicine, Brookdale Department of Molecular, Cell and Developmental Biology, Box 1020, One Gustave 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 15 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2007, p. 8547-8560, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00589-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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