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CTCF is a barrier for 2C-like reprogramming.

Teresa Olbrich1, Maria Vega-Sendino1, Desiree Tillo2

  • 1Laboratory of Genome Integrity, CCR, NCI, NIH, Bethesda, MD, USA.

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|August 12, 2021
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Summary
This summary is machine-generated.

CCCTC-binding factor (CTCF) acts as a barrier to totipotent-like cell reprogramming in mouse ESCs. CTCF depletion promotes 2C-like cell conversion, which is reversible and specific to pluripotent cells, highlighting CTCF

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Area of Science:

  • Cell biology
  • Developmental biology
  • Epigenetics

Background:

  • Totipotent cells can form all embryonic and extra-embryonic tissues.
  • 2 cell (2C)-like cells, rare cells with totipotent potential, exist in embryonic stem cell (ESC) cultures.
  • The molecular mechanisms driving 2C-like cell reprogramming are not fully understood.

Purpose of the Study:

  • To investigate the role of CCCTC-binding factor (CTCF) in 2C-like cell reprogramming.
  • To elucidate the molecular determinants of the conversion to a 2C-like state.

Main Methods:

  • Investigated the effect of CTCF depletion on ESCs.
  • Analyzed DNA damage at CTCF binding sites during DUX-induced reprogramming.
  • Assessed the specificity of CTCF depletion effects in neural progenitor cells.
  • Examined the necessity of ZSCAN4 cluster activation for reprogramming.

Main Results:

  • CTCF acts as a barrier to 2C-like reprogramming.
  • DUX-induced 2C-like conversion involves DNA damage at CTCF binding sites.
  • CTCF depletion in ESCs promotes spontaneous, reversible 2C-like cell conversion.
  • This reprogramming is specific to pluripotent cells.
  • ZSCAN4 cluster activation is essential for 2C-like reprogramming.

Conclusions:

  • CTCF is an unexpected barrier to 2C-like cell reprogramming.
  • CTCF levels regulate the conversion of ESCs to a totipotent-like state.
  • Understanding CTCF's role offers insights into controlling cell fate and pluripotency.