AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation

Cell. 2014 Oct 23;159(3):558-71. doi: 10.1016/j.cell.2014.09.049.


The recognition of modified histones by "reader" proteins constitutes a key mechanism regulating gene expression in the chromatin context. Compared with the great variety of readers for histone methylation, few protein modules that recognize histone acetylation are known. Here, we show that the AF9 YEATS domain binds strongly to histone H3K9 acetylation and, to a lesser extent, H3K27 and H3K18 acetylation. Crystal structural studies revealed that AF9 YEATS adopts an eight-stranded immunoglobin fold and utilizes a serine-lined aromatic "sandwiching" cage for acetyllysine readout, representing a novel recognition mechanism that is distinct from that of known acetyllysine readers. ChIP-seq experiments revealed a strong colocalization of AF9 and H3K9 acetylation genome-wide, which is important for the chromatin recruitment of the H3K79 methyltransferase DOT1L. Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.

Publication types

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

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Gene Expression Regulation
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / metabolism
  • Histone Code*
  • Histone-Lysine N-Methyltransferase
  • Histones / metabolism
  • Humans
  • Methylation
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Alignment
  • Transcription, Genetic


  • Histones
  • MLLT3 protein, human
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • YAF9 protein, S cerevisiae
  • DOT1L protein, human
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Histone Acetyltransferases

Associated data

  • GEO/GSE60366
  • PDB/4TMP