TY - JOUR
T1 - ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα
AU - Gonzalez, David
AU - Luyten, Annouck
AU - Bartholdy, Boris
AU - Zhou, Qiling
AU - Kardosova, Miroslava
AU - Ebralidze, Alex
AU - Swanson, Kenneth D.
AU - Radomska, Hanna S.
AU - Zhang, Pu
AU - Kobayashi, Susumu S.
AU - Welner, Robert S.
AU - Levantini, Elena
AU - Steidl, Ulrich
AU - Chong, Gilbert
AU - Collombet, Samuel
AU - Choi, Min Hee
AU - Friedman, Alan D.
AU - Scott, Linda M.
AU - Alberich-Jorda, Meritxell
AU - Tenen, Daniel G.
N1 - Funding Information:
2Supported by National Institutes of Health Grants R21CA178301 and R01CA169259, American Cancer Society Grant RSG-13-047-01, and Har-vard Stem Cell Institute Grant DP-0110-12-00.
Funding Information:
This work was supported by the Singapore Ministry of Health’s National Med-ical Research Council under its Singapore Translational Research (STaR) Investigator Award (to D. G. T.) and by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative; National Institutes of Health Grants HL131477 and CA66996 (to D. G. T.); institutional funding from the IMG AS CR (RVO 68378050) (to M. A.-J.); and German Research Foundation (DFG) Grant BA 3771/1-1 (to B. B.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the respon-sibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017/11/17
Y1 - 2017/11/17
N2 - 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 mechanismthat is distinctfromthat observed in liver cellsandadipocytes. Altogether, our data suggest that ZNF143 plays an important role in the expression of C/EBPα in myeloid cells.
AB - 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 mechanismthat is distinctfromthat observed in liver cellsandadipocytes. Altogether, our data suggest that ZNF143 plays an important role in the expression of C/EBPα in myeloid cells.
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U2 - 10.1074/jbc.M117.811109
DO - 10.1074/jbc.M117.811109
M3 - Article
C2 - 28900037
AN - SCOPUS:85034570642
SN - 0021-9258
VL - 292
SP - 18924
EP - 18936
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -