Histone h3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells

Mol Cell. 2009 Feb 27;33(4):417-27. doi: 10.1016/j.molcel.2009.02.004.


Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Chromatin Immunoprecipitation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Gene Regulatory Networks*
  • Genome, Human
  • Histones / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Lysine / chemistry
  • Lysine / metabolism*
  • Mice
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Protein Processing, Post-Translational / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism


  • Histones
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Lysine

Associated data

  • GEO/GSE14749