H3K4me3, H3K9ac, H3K27ac, H3K27me3 and H3K9me3 Histone Tags Suggest Distinct Regulatory Evolution of Open and Condensed Chromatin Landmarks

Cells. 2019 Sep 5;8(9):1034. doi: 10.3390/cells8091034.


Background: Transposons are selfish genetic elements that self-reproduce in host DNA. They were active during evolutionary history and now occupy almost half of mammalian genomes. Close insertions of transposons reshaped structure and regulation of many genes considerably. Co-evolution of transposons and host DNA frequently results in the formation of new regulatory regions. Previously we published a concept that the proportion of functional features held by transposons positively correlates with the rate of regulatory evolution of the respective genes.

Methods: We ranked human genes and molecular pathways according to their regulatory evolution rates based on high throughput genome-wide data on five histone modifications (H3K4me3, H3K9ac, H3K27ac, H3K27me3, H3K9me3) linked with transposons for five human cell lines.

Results: Based on the total of approximately 1.5 million histone tags, we ranked regulatory evolution rates for 25075 human genes and 3121 molecular pathways and identified groups of molecular processes that showed signs of either fast or slow regulatory evolution. However, histone tags showed different regulatory patterns and formed two distinct clusters: promoter/active chromatin tags (H3K4me3, H3K9ac, H3K27ac) vs. heterochromatin tags (H3K27me3, H3K9me3).

Conclusion: In humans, transposon-linked histone marks evolved in a coordinated way depending on their functional roles.

Keywords: chromatin structure; epigenetics; gene ontology; gene regulation; histone modifications; human genome molecular evolution; molecular pathway analysis; promoter; retrotransposons; transposable elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / chemistry
  • Chromatin / genetics*
  • Chromatin Assembly and Disassembly
  • DNA Transposable Elements
  • Evolution, Molecular*
  • Histone Code*
  • Histones / chemistry
  • Histones / genetics*
  • Humans
  • Models, Genetic


  • Chromatin
  • DNA Transposable Elements
  • Histones