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Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency.

Cell stem cell | 2018

As somatic cells are converted into induced pluripotent stem cells (iPSCs), their chromatin is remodeled to a pluripotent configuration with unique euchromatin-to-heterochromatin ratios, DNA methylation patterns, and enhancer and promoter status. The molecular machinery underlying this process is largely unknown. Here, we show that embryonic stem cell (ESC)-specific factors Dppa2 and Dppa4 play a key role in resetting the epigenome to a pluripotent state. They are induced in reprogramming intermediates, function as a heterodimer, and are required for efficient reprogramming of mouse and human cells. When co-expressed with Oct4, Klf4, Sox2, and Myc (OKSM) factors, Dppa2/4 yield reprogramming efficiencies that exceed 80% and accelerate reprogramming kinetics, generating iPSCs in 2 to 4 days. When bound to chromatin, Dppa2/4 initiate global chromatin decompaction via the DNA damage response pathway and contribute to downregulation of somatic genes and activation of ESC enhancers, all of which enables an efficient transition to pluripotency. Our work provides critical insights into how the epigenome is remodeled during acquisition of pluripotency.

Pubmed ID: 30146411 RIS Download

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Antibodies used in this publication

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM105772
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM107092
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027990
  • Agency: NIH HHS, United States
    Id: S10 OD018521
  • Agency: NIGMS NIH HHS, United States
    Id: DP2 GM123507

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