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Paper Chase

ZNF143 is an important regulator of the myeloid transcription factor C/EBPα.

J. Biol. Chem.. Sep 12, 2017.
Gonzalez D, Luyten A, Bartholdy B, Zhou Q, Kardosova M, Ebralidze A, Swanson KD, Radomska H, Zhang P, Kobayashi SS, Welner RS, Levantini E, Steidl U, Chong G, Collombet S, Choi MH, Friedman AD, Scott LM, Alberich-Jorda M, Tenen DG.

National University of Singapore, Singapore; csidgt@nus.edu.sg.

Abstract:

The transcription factor (TF) C/EBPα is essential for myeloid differentiation and is frequently dysregulated in acute myeloid leukemia (AML). While 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, approximately 100 bases upstream of the CEBPA transcription start site (TSS), 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, chicken and frog, 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 8bp 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 suggests that ZNF143 plays an important role in the expression of C/EBPα in myeloid cells.