title: Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Electronic address: whu@wi.mit.edu.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Hu
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology and Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D025461:Feedback, Physiological; D050982:GATA1 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C477604:Cpeb4 protein, mouse; C494436:Elf3 protein, mouse; C494689:Gata1 protein, mouse; C489366:Tal1 protein, mouse