Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis.

Abstract:

: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-2beta 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.

journal_name

Mol Cell Biol

authors

Siatecka M,Xue L,Bieker JJ

doi

10.1128/MCB.00589-07

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

8547-60

issue

24

eissn

0270-7306

issn

1098-5549

pii

MCB.00589-07

journal_volume

27

pub_type

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