Epigenetic Markings

Epigenetic markings are changes to DNA or its packaging components that alter gene expression, effectively turning gene transcription on and off, and that are inherited by daughter cells. Commonly studied epigenetic modifications are CpG dinucleotide methylation, which are often concentrated at Alu and SVA sequences (one estimate asserts that over 30% of all CpG sites are within Alu sequences), and modifications of histones. While research examining these patterns of epigenetic modifications has found that patterns are largely conserved across species, human-specific alterations have also been found, and a recent study discovered hundreds of DNase1 hypersensitive sites (DHS, which denote regions of gene regulation) that have been uniquely lost or gained in the human and chimpanzee lineages, using macaque as an outgroup. These differences were associated with changes in chromatin accessibility and gene expression. Other studies have found that methylation patterns vary between humans and non-human primates both at the global and individual gene level, and that these patterns correlate to species-specific gene expression.

Differences between species also exist in other histone modification patterns, which again correspond to changes in expression. A recent study examining H3K27ac and H3K4me2 histone modification during corticogenesis identified promoters and enhancers gained in humans versus macaque and mouse. Gains were highly associated with genes involved in neuronal proliferation, migration, and cortical-map organization. While estimates of the degree to which these modifications are responsible for species-specific expression patterns are moderate (~10% of the variance explained), these epigenetic modifications have the potential to explain some of the human phenotypic uniqueness that cannot be attributed to changes in DNA sequence.