Epigenetic mechanisms of partial dosage compensation in an avian, female heterogametic system

The evolution of genetic sex determination is often accompanied by degradation of one of the proto sex chromosomes. Male heterogametic systems have evolved convergent, epigenetic mechanisms restoring the resulting imbalance in gene dosage between diploid autosomes (AA) and the hemizygous sex chromosome (X). Female heterogametic systems (AA_f ZW_f, AA_m ZZ_m) tend to only show partial dosage compensation (0.5 &lt; Z_f:AA_f &lt; 1) and dosage balance (0.5f:ZZ_m&lt;1). The underlying mechanism remains largely elusive. Here, we quantified gene expression for a total of 15 male and female Eurasian crows (<em>Corvus (corone) spp</em>.) raised under common garden conditions. In addition, we characterized aspects of the regulatory landscape quantifying genome-wide ATAC-seq and 5mC methylation profiles. Partial dosage compensation was explained by female upregulation of Z-linked genes accompanied by increased chromatin accessibility on the female Z chromosome. 5mC methylation was strongly reduced in open chromatin-regions and GC islands and showed chromosome-, but no sex-specific variation. With the exception of the pseudo-autosomal region (PAR), female upregulation of gene expression was evenly spread across the Z chromosome without evidence for regional epigenetic regulation, as has for example been suggested for the male hypermethylated region (MHM) in chicken. Our results support the hypothesis that partial dosage compensation in female heterogametic systems is subject to chromosome-wide, epigenetic control mediated by differential chromatin accessibility between the sexes.