DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.

Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. We show that embryonic stem cells (ESCs) mainly express DIDO3 and that their differentiation after leukemia inhibitory factor withdrawal requires DIDO1 expression. C-terminal truncation of DIDO3 (Dido3ΔCT) impedes ESC differentiation while retaining self-renewal; small hairpin RNA-Dido1 ...
ESCs have the same phenotype. Dido3ΔCT ESC differentiation is rescued by ectopic expression of DIDO3, which binds the Dido locus via H3K4me3 and RNA POL II and induces DIDO1 expression. DIDO1, which is exported to cytoplasm, associates with, and is N-terminally phosphorylated by PKCiota. It binds the E3 ubiquitin ligase WWP2, which contributes to cell fate by OCT4 degradation, to allow expression of primitive endoderm (PE) markers. PE formation also depends on phosphorylated DIDO3 localization to centrosomes, which ensures their correct positioning for PE cell polarization. We propose that DIDO isoforms act as a switchboard that regulates genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Differentiation, Cell Line, Cell Polarity, Cell Proliferation, DNA-Binding Proteins, Endoderm, Gene Expression Regulation, Developmental, Mice, Mouse Embryonic Stem Cells, Octamer Transcription Factor-3, Protein Interaction Maps, Protein Isoforms, Protein Transport, Proteolysis, Transcription Factors, Ubiquitin-Protein Ligases
Stem Cell Reports
Date: Dec. 11, 2016
Download Curated Data For This Publication
211314
Switch View:
  • Interactions 5