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

David Gonzalez, Annouck Luyten, Boris A. Bartholdy, Qiling Zhou, Miroslava Kardosova, Alex Ebralidze, Kenneth D. Swanson, Hanna S. Radomska, Pu Zhang, Susumu S. Kobayashi, Robert S. Welner, Elena Levantini, Ulrich G. Steidl, Gilbert Chong, Samuel Collombet, Min Hee Choi, Alan D. Friedman, Linda M. Scott, Meritxell Alberich-Jorda, Daniel G. Tenen

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)18924-18936
Number of pages13
JournalJournal of Biological Chemistry
Volume292
Issue number46
DOIs
StatePublished - Jan 1 2017

Fingerprint

Gene encoding
Transcription Initiation Site
Myeloid Cells
Liver
Transcription Factors
Genes
Chemical activation
Conserved Sequence
Xenopus
Acute Myeloid Leukemia
Anura
Transcriptional Activation
Sequence Analysis
Chickens
Rodentia
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gonzalez, D., Luyten, A., Bartholdy, B. A., Zhou, Q., Kardosova, M., Ebralidze, A., ... Tenen, D. G. (2017). ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα. Journal of Biological Chemistry, 292(46), 18924-18936. https://doi.org/10.1074/jbc.M117.811109

ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα. / Gonzalez, David; Luyten, Annouck; Bartholdy, Boris A.; Zhou, Qiling; Kardosova, Miroslava; Ebralidze, Alex; Swanson, Kenneth D.; Radomska, Hanna S.; Zhang, Pu; Kobayashi, Susumu S.; Welner, Robert S.; Levantini, Elena; Steidl, Ulrich G.; Chong, Gilbert; Collombet, Samuel; Choi, Min Hee; Friedman, Alan D.; Scott, Linda M.; Alberich-Jorda, Meritxell; Tenen, Daniel G.

In: Journal of Biological Chemistry, Vol. 292, No. 46, 01.01.2017, p. 18924-18936.

Research output: Contribution to journalArticle

Gonzalez, D, Luyten, A, Bartholdy, BA, Zhou, Q, Kardosova, M, Ebralidze, A, Swanson, KD, Radomska, HS, Zhang, P, Kobayashi, SS, Welner, RS, Levantini, E, Steidl, UG, Chong, G, Collombet, S, Choi, MH, Friedman, AD, Scott, LM, Alberich-Jorda, M & Tenen, DG 2017, 'ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα', Journal of Biological Chemistry, vol. 292, no. 46, pp. 18924-18936. https://doi.org/10.1074/jbc.M117.811109
Gonzalez, David ; Luyten, Annouck ; Bartholdy, Boris A. ; Zhou, Qiling ; Kardosova, Miroslava ; Ebralidze, Alex ; Swanson, Kenneth D. ; Radomska, Hanna S. ; Zhang, Pu ; Kobayashi, Susumu S. ; Welner, Robert S. ; Levantini, Elena ; Steidl, Ulrich G. ; Chong, Gilbert ; Collombet, Samuel ; Choi, Min Hee ; Friedman, Alan D. ; Scott, Linda M. ; Alberich-Jorda, Meritxell ; Tenen, Daniel G. / ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 46. pp. 18924-18936.
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AU - Kardosova, Miroslava

AU - Ebralidze, Alex

AU - Swanson, Kenneth D.

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AU - Zhang, Pu

AU - Kobayashi, Susumu S.

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AU - Steidl, Ulrich G.

AU - Chong, Gilbert

AU - Collombet, Samuel

AU - Choi, Min Hee

AU - Friedman, Alan D.

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AU - Alberich-Jorda, Meritxell

AU - Tenen, Daniel G.

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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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