4.4 Review

Emerging roles of the histone chaperone CAF-1 in cellular plasticity

Journal

CURRENT OPINION IN GENETICS & DEVELOPMENT
Volume 46, Issue -, Pages 83-94

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2017.06.004

Keywords

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Funding

  1. MGH
  2. NIH [R01 HD058013-06, P01 GM099134-06]
  3. Gerald and Darlene Jordan Chair in Regenerative Medicine
  4. Department of Defense Peer-Reviewed Cancer Research Program visionary postdoctoral fellowship [CA120212]
  5. Massachusetts General Hospital ECOR Tosteson Fund for Medical Discovery fellowship

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During embryonic development, cells become progressively restricted in their differentiation potential. This is thought to be regulated by dynamic changes in chromatin structure and associated modifications, which act together to stabilize distinct specialized cell lineages. Remarkably, differentiated cells can be experimentally reprogrammed to a stem cell-like state or to alternative lineages. Thus, cellular reprogramming provides a valuable platform to study the mechanisms that normally safeguard cell identity and uncover factors whose manipulation facilitates cell fate transitions. Recent work has identified the chromatin assembly factor complex CAF-1 as a potent barrier to cellular reprogramming. In addition, CAF-1 has been implicated in the reversion of pluripotent cells to a totipotent-like state and in various lineage conversion paradigms, suggesting that modulation of CAF-1 levels may endow cells with a developmentally more plastic state. Here, we review these exciting results, discuss potential mechanisms and speculate on the possibility of exploiting chromatin assembly pathways to manipulate cell identity.

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