Establishment and evolution of heterochromatin.

The eukaryotic genome is packaged into transcriptionally active euchromatin and silent heterochromatin, with most studies focused on the former encompassing the majority of protein-coding genes. The recent development of various sequencing techniques has refined this classic dichromatic partition and has better illuminated the composition, establishment, and evolution of this genomic and epigenomic "dark matter" in the context of topologically associated domains and phase-separated droplets. Heterochromatin includes genomic regions that can be densely stained by chemical dyes, which have been shown to be enriched for repetitive elements and epigenetic marks, including H3K9me2/3 and H3K27me3. Heterochromatin is usually replicated late, concentrated at the nuclear periphery or around nucleoli, and usually lacks highly expressed genes; and now it is considered to be as neither genetically inert nor developmentally static. Heterochromatin guards genome integrity against transposon activities and exerts important regulatory functions by targeting beyond its contained genes. Both its nucleotide sequences and regulatory proteins exhibit rapid coevolution between species. In addition, there are dynamic transitions between euchromatin and heterochromatin during developmental and evolutionary processes. We summarize here the ever-changing characteristics of heterochromatin and propose models and principles for the evolutionary transitions of heterochromatin that have been mainly learned from studies of Drosophila and yeast. Finally, we highlight the role of sex chromosomes in studying heterochromatin evolution.