Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells

Nucleic Acids Res. 2017 Sep 29;45(17):10103-10114. doi: 10.1093/nar/gkx692.


Direct reprogramming can be achieved by forced expression of master transcription factors. Yet how such factors mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Through embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS cell-specific 'CAG' factors (Cdx2, Arid3a and Gata3), we interrogate their chromosomal target occupancies, modulation of global transcription and chromatin accessibility at the initial stage of reprogramming. From the studies, we uncover a sequential, two-step mechanism of cellular reprogramming in which repression of pre-existing ES cell-associated gene expression program is followed by activation of TS cell-specific genes by CAG factors. Therefore, we reveal that CAG factors function as both decommission and pioneer factors during ES to TS-like cell fate conversion.

MeSH terms

  • Animals
  • CDX2 Transcription Factor / genetics
  • CDX2 Transcription Factor / physiology*
  • Cells, Cultured
  • Cellular Reprogramming Techniques*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Culture Media, Conditioned
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Embryonic Stem Cells / cytology*
  • Enhancer Elements, Genetic
  • Fibroblasts
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / physiology*
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Histone Code
  • Mice
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Trophoblasts / cytology*


  • Arid3a protein, mouse
  • CDX2 Transcription Factor
  • Cdx2 protein, mouse
  • Chromatin
  • Culture Media, Conditioned
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Transcription Factors