Histone H3 lysine 4 methylation patterns in higher eukaryotic genes

Nat Cell Biol. 2004 Jan;6(1):73-7. doi: 10.1038/ncb1076. Epub 2003 Dec 7.


Lysine residues within histones can be mono-, di - or tri-methylated. In Saccharomyces cerevisiae tri-methylation of Lys 4 of histone H3 (K4/H3) correlates with transcriptional activity, but little is known about this methylation state in higher eukaryotes. Here, we examine the K4/H3 methylation pattern at the promoter and transcribed region of metazoan genes. We analysed chicken genes that are developmentally regulated, constitutively active or inactive. We found that the pattern of K4/H3 methylation shows similarities to S. cerevisiae. Tri-methyl K4/H3 peaks in the 5' transcribed region and active genes can be discriminated by high levels of tri-methyl K4/H3 compared with inactive genes. However, our results also identify clear differences compared to yeast, as significant levels of K4/H3 methylation are present on inactive genes within the beta-globin locus, implicating this modification in maintaining a 'poised' chromatin state. In addition, K4/H3 di-methylation is not genome-wide and di-methylation is not uniformly distributed throughout the transcribed region. These results indicate that in metazoa, di- and tri-methylation of K4/H3 is linked to active transcription and that significant differences exist in the genome-wide methylation pattern as compared with S. cerevisiae.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chickens
  • Chromosome Mapping
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation / genetics*
  • Genes / genetics
  • Genome
  • Globins / genetics
  • Histones / metabolism*
  • Lysine / metabolism*
  • Methylation*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Transcriptional Activation / genetics


  • Histones
  • Globins
  • Lysine