| Literature DB >> 28900037 |
David Gonzalez1,2, Annouck Luyten1, Boris Bartholdy2, Qiling Zhou1, Miroslava Kardosova3,4, Alex Ebralidze2, Kenneth D Swanson5, Hanna S Radomska2,6, Pu Zhang2, Susumu S Kobayashi2,5, Robert S Welner2,7, Elena Levantini2,8, Ulrich Steidl2,9, Gilbert Chong1, Samuel Collombet1, Min Hee Choi1, Alan D Friedman10, Linda M Scott11, Meritxell Alberich-Jorda12,4, Daniel G Tenen13,2.
Abstract
The transcription factor C/EBPα is essential for myeloid differentiation and is frequently dysregulated in acute myeloid leukemia. Although studied extensively, the precise regulation of its gene by upstream factors has remained largely elusive. Here, we investigated its transcriptional activation during myeloid differentiation. We identified an evolutionarily conserved octameric sequence, CCCAGCAG, ∼100 bases upstream of the CEBPA transcription start site, and demonstrated through mutational analysis that this sequence is crucial for C/EBPα expression. This sequence is present in the genes encoding C/EBPα in humans, rodents, chickens, and frogs and is also present in the promoters of other C/EBP family members. We identified that ZNF143, the human homolog of the Xenopus transcriptional activator STAF, specifically binds to this 8-bp sequence to activate C/EBPα expression in myeloid cells through a mechanism that is distinct from that observed in liver cells and adipocytes. Altogether, our data suggest that ZNF143 plays an important role in the expression of C/EBPα in myeloid cells.Entities:
Keywords: C/EBPalpha; CCAAT-enhancer-binding protein (C/EBP); ZNF143; gene regulation; hematopoiesis; promoter; transcription factor
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Year: 2017 PMID： 28900037 PMCID： PMC5704476 DOI： 10.1074/jbc.M117.811109
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157