SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal

Epigenetics. 2013 Feb;8(2):177-83. doi: 10.4161/epi.23416. Epub 2013 Jan 16.


The histone H2A variant H2AZ is an essential chromatin signaling factor. Herein, we report that H2AZ is monomethylated at lysine 7 (H2AZK7me1) by the lysine methyltransferase SETD6. We observed that methylation of H2AZ increased noticeably upon cellular differentiation of mouse embryonic stem cells (mESCs). H2AZK7me1 and the repressive H3K27me3 mark were found near the transcriptional start sites of differentiation marker genes, but were removed upon retinoic acid-induced cellular differentiation. The depletion of Setd6 in mESCs led to cellular differentiation, compromised self-renewal, and poor clonogenicity. These findings demonstrate that mESCs require Setd6 for self-renewal and portray H2AZK7me1 as a marker of cellular differentiation.

Keywords: H2AZ; SETD6; embryonic stem cells; histone variant; lysine methylation; lysine methyltransferase.

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

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Embryonic Stem Cells / physiology*
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Mice
  • Molecular Sequence Data
  • Protein Methyltransferases / genetics
  • Protein Methyltransferases / metabolism*
  • Tretinoin / pharmacology


  • Histones
  • histone H2A.F-Z
  • Tretinoin
  • Protein Methyltransferases
  • SETD6 protein, human
  • SETD6 protein, mouse
  • Lysine