Pluripotency Activity of Nanog Requires Biochemical Stabilization by Variant Histone Protein H2A.Z

Stem Cells. 2015 Jul;33(7):2126-34. doi: 10.1002/stem.2011. Epub 2015 May 21.

Abstract

The variant histone protein H2A.Z plays a critical role in early development. Likewise, Nanog, a master regulator of embryonic stem cells (ESCs), is essential for proper development in early embryogenesis. In this study, we establish that these two factors work together to maintain pluripotency. It is shown that H2A.Z influences the protein level of Nanog through the ubiquitin-proteasome pathway. Knockdown of H2A.Z causes differentiation of mouse ESCs and disrupts the reprogramming of somatic cells, which can be partially rescued by overexpression of Nanog. We conclude that the H2A.Z-Nanog partnership is involved in ESC pluripotency and reprogramming of somatic cells. Stem Cells 2015;33:2126-2134.

Keywords: Differentiation of stem cells; H2A.Z; Induced pluripotent stem cells; Ubiquitination of Nanog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Histones / metabolism*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Nanog Homeobox Protein
  • Pluripotent Stem Cells / metabolism

Substances

  • Histones
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein