Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells

EMBO J. 2013 Jul 17;32(14):1990-2000. doi: 10.1038/emboj.2013.110. Epub 2013 May 14.


While the Polycomb complex is known to regulate cell identity in ES cells, its role in controlling tissue-specific stem cells is not well understood. Here we show that removal of Ezh1 and Ezh2, key Polycomb subunits, from mouse skin results in a marked change in fate determination in epidermal progenitor cells, leading to an increase in the number of lineage-committed Merkel cells, a specialized subtype of skin cells involved in mechanotransduction. By dissecting the genetic mechanism, we showed that the Polycomb complex restricts differentiation of epidermal progenitor cells by repressing the transcription factor Sox2. Ablation of Sox2 results in a dramatic loss of Merkel cells, indicating that Sox2 is a critical regulator of Merkel cell specification. We show that Sox2 directly activates Atoh1, the obligate regulator of Merkel cell differentiation. Concordantly, ablation of Sox2 attenuated the Ezh1/2-null phenotype, confirming the importance of Polycomb-mediated repression of Sox2 in maintaining the epidermal progenitor cell state. Together, these findings define a novel regulatory network by which the Polycomb complex maintains the progenitor cell state and governs differentiation in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression Regulation, Developmental
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Merkel Cells / cytology*
  • Merkel Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Polycomb Repressive Complex 2 / deficiency
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Pregnancy
  • SOXB1 Transcription Factors / deficiency
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • LIM-Homeodomain Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh1 protein, mouse
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2