Integrative mapping of the dog epigenome: Reference annotation for comparative intertissue and cross-species studies

Sci Adv. 2023 Jul 7;9(27):eade3399. doi: 10.1126/sciadv.ade3399. Epub 2023 Jul 5.

Abstract

Dogs have become a valuable model in exploring multifaceted diseases and biology relevant to human health. Despite large-scale dog genome projects producing high-quality draft references, a comprehensive annotation of functional elements is still lacking. We addressed this through integrative next-generation sequencing of transcriptomes paired with five histone marks and DNA methylome profiling across 11 tissue types, deciphering the dog's epigenetic code by defining distinct chromatin states, super-enhancer, and methylome landscapes, and thus showed that these regions are associated with a wide range of biological functions and cell/tissue identity. In addition, we confirmed that the phenotype-associated variants are enriched in tissue-specific regulatory regions and, therefore, the tissue of origin of the variants can be traced. Ultimately, we delineated conserved and dynamic epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog that can be used for comparative biology and medical research.

MeSH terms

  • Animals
  • Chromatin* / genetics
  • Dogs
  • Epigenesis, Genetic
  • Epigenome*
  • Epigenomics
  • Genome
  • Histone Code
  • Regulatory Sequences, Nucleic Acid

Substances

  • Chromatin