Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology

Cells. 2019 Oct 8;8(10):1219. doi: 10.3390/cells8101219.

Abstract

Background: Retroelements (REs) are mobile genetic elements comprising ~40% of human DNA. They can reshape expression patterns of nearby genes by providing various regulatory sequences. The proportion of regulatory sequences held by REs can serve a measure of regulatory evolution rate of the respective genes and molecular pathways.

Methods: We calculated RE-linked enrichment scores for individual genes and molecular pathways based on ENCODE project epigenome data for enhancer-specific histone modification H3K4me1 in five human cell lines. We identified consensus groups of molecular processes that are enriched and deficient in RE-linked H3K4me1 regulation.

Results: We calculated H3K4me1 RE-linked enrichment scores for 24,070 human genes and 3095 molecular pathways. We ranked genes and pathways and identified those statistically significantly enriched and deficient in H3K4me1 RE-linked regulation.

Conclusion: Non-coding RNA genes were statistically significantly enriched by RE-linked H3K4me1 regulatory modules, thus suggesting their high regulatory evolution rate. The processes of gene silencing by small RNAs, DNA metabolism/chromatin structure, sensory perception/neurotransmission and lipids metabolism showed signs of the fastest regulatory evolution, while the slowest processes were connected with immunity, protein ubiquitination/degradation, cell adhesion, migration and interaction, metals metabolism/ion transport, cell death, intracellular signaling pathways.

Keywords: H3K4me1; enhancers of transcription; epigenetics; gene expression regulation; gene ontology; histone modifications; human genome evolution; molecular pathways; retroelements; retrotransposons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic
  • Evolution, Molecular*
  • Genome, Human*
  • Histone Code*
  • Humans
  • Retroelements*

Substances

  • Retroelements