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Title: C/EBPα and DEK coordinately regulate myeloid differentiation
Authors: Koleva, R.I.
Ficarro, S.B.
Radomska, H.S.
Carrasco-Alfonso, M.J.
Alberta, J.A.
Webber, J.T.
Luckey, C.J.
Marcucci, G.
Tenen, D.G. 
Marto, J.A.
Issue Date: 24-May-2012
Citation: Koleva, R.I., Ficarro, S.B., Radomska, H.S., Carrasco-Alfonso, M.J., Alberta, J.A., Webber, J.T., Luckey, C.J., Marcucci, G., Tenen, D.G., Marto, J.A. (2012-05-24). C/EBPα and DEK coordinately regulate myeloid differentiation. Blood 119 (21) : 4878-4888. ScholarBank@NUS Repository.
Abstract: The transcription factor C/EBPα is a critical mediator of myeloid differentiation and is often functionally impaired in acute myeloid leukemia. Recent studies have suggested that oncogenic FLT3 activity disrupts wild-type C/EBPα function via phosphorylation on serine 21 (S21). Despite the apparent role of pS21 as a negative regulator of C/EBPα transcription activity, the mechanism by which phosphorylation tips the balance between transcriptionally competent and inhibited forms remains unresolved. In the present study, we used immuno-affinity purification combined with quantitative mass spectrometry to delineate the proteins associated with C/EBPα on chromatin. We identified DEK, a protein with genetic links to leukemia, as a member of the C/EBPα complexes, and demonstrate that this association is disrupted by S21 phosphorylation. We confirmed that DEK is recruited specifically to chromatin with C/EBPα to enhance GCSFR3 promoter activation. In addition, we demonstrated that genetic depletion of DEK reduces the ability of C/EBPα to drive the expression of granulocytic target genes in vitro and disrupts G-CSF-mediated granulocytic differentiation of fresh human BM-derived CD34 + cells. Our data suggest that C/EBPα and DEK coordinately activate myeloid gene expression and that S21 phosphorylation on wild-type C/EBPαmediates protein interactions that regulate the differentiation capacity of hematopoietic progenitors. © 2012 by The American Society of Hematology.
Source Title: Blood
ISSN: 00064971
DOI: 10.1182/blood-2011-10-383083
Appears in Collections:Staff Publications

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