Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis.
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.
Siatecka
Miroslawa
M
Mount Sinai School of Medicine, Brookdale Department of Molecular, Cell and Developmental Biology, Box 1020, One Gustave Levy Place, New York, NY 10029, USA.
Xue
Li
L
Bieker
James J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D051741:Kruppel-Like Transcription Factors; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C080774:erythroid Kruppel-like factor; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D008239:Lysine