Genomic and epigenomic maps of mouse centromeres and pericentromeres

Abstract

Satellite DNA makes up [~]11% of the mouse genome, predominantly located in centromeric and pericentric regions, which are crucial for chromosome segregation. While comprehensive assemblies of these regions have been established in the human genome, they are still lacking in the mouse genome. In this study, we used PacBio long-read sequencing, CUT&RUN sequencing, DNA methylation analysis, and RNA sequencing to generate genomic and epigenomic maps of these regions. We find that centromeric regions are primarily occupied by 120-mer Minor satellites, with other Minor Satellite length variants, 112-mers and 112-64-dimers, localized at centromere-pericentric junctions. Pericentromeric regions are mainly composed of homogeneous Major satellites, while pericentric-chromosomal junctions contain a higher density of divergent satellites. Additionally, the density of non-satellite repeats increases progressively from centromeres to pericentromeres, and further toward chromosomal arm junctions. We found that 120-mer Minor satellites in the core centromere are highly enriched with CENP-A, while the 112-mers and 112-64-dimers show lower CENP-A levels. Homogeneous Major satellites are more enriched with H3K9me3 heterochromatin, whereas divergent Major satellites are preferentially associated with H3K27me3. Furthermore, DNA methylation levels are lower in centromeres compared to pericentric regions. We also observed that only a small subset of satellites is transcribed into RNA, particularly regions exhibiting lower DNA methylation density. Our comprehensive assembly and characterization of the genomic and epigenomic landscape of mouse centromeric and pericentric regions have major implications for satellite biology and ongoing mouse telomere-to-telomere (T2T) assembly efforts.