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Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.

Wenqian Hu | Bingbing Yuan | Harvey F Lodish
Developmental cell | 2014

While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation.

Pubmed ID: 25220394

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01DK068348
  • Agency: NHLBI NIH HHS, United States
    Id: K99 HL118157
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL032262
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK068348
  • Agency: NHLBI NIH HHS, United States
    Id: 1K99HL118157
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL066105
  • Agency: NHLBI NIH HHS, United States
    Id: 5P01HL066105

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DAVID (tool)

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RRID:SCR_002473

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RRID:SCR_010236

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RRID:SCR_006158

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