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p27(Kip1) directly represses Sox2 during embryonic stem cell differentiation

Han Li1, Manuel Collado, Aranzazu Villasante

  • 1Tumor Suppression Group, Spanish National Cancer Research Centre, Madrid, E28029, Spain.

Cell Stem Cell
|December 11, 2012
PubMed

Insights

The tumor suppressor p27 (also known as CDKN1B) is crucial for repressing the pluripotency gene Sox2 during cell differentiation. Loss of p27 facilitates reprogramming and impacts development and cancer.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Transcriptional silencing of pluripotency genes is key for cell differentiation.
  • Mechanisms controlling Sox2 expression during differentiation are not fully understood.

Purpose of the Study:

  • To investigate the role of the tumor suppressor p27 in regulating Sox2 expression.
  • To explore the implications of the p27-Sox2 interaction in cell reprogramming and disease.

Main Methods:

  • Analysis of p27 null mice and derived induced pluripotent stem cells (iPSCs).
  • Chromatin immunoprecipitation to identify protein-DNA interactions at the Sox2 locus.
  • Genetic rescue experiments using Sox2 haploinsufficiency.

Main Results:

  • p27 null cells exhibit elevated basal Sox2 expression and impaired Sox2 repression during differentiation.
  • p27 interacts with a p130-E2F4-SIN3A complex at the Sox2 SRR2 enhancer.
  • Sox2 haploinsufficiency ameliorates p27 null phenotypes, including gigantism and tumors.

Conclusions:

  • p27 acts as a critical repressor of Sox2 during differentiation.
  • The p27-Sox2 axis is vital for normal development, cell reprogramming, and cancer prevention.
  • Dysregulation of p27 impacts human pathologies associated with germline mutations.

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