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The Zhongwei goat is kept primarily for its beautiful white, curly pelt that appears when the kid is approximately 1 month old; however, this representative phenotype often changes to a less curly phenotype during postnatal development in a process that may be mediated by multiple molecular signals. DNA methylation plays important roles in mammalian cellular processes and is essential for the initiation of hair follicle (HF) development. Here, we sought to investigate the effects of genome-wide DNA methylation by combining expression profiles of the underlying curly fleece dynamics. Genome-wide DNA methylation maps and transcriptomes of skin tissues collected from 45- to 108-day-old goats were used for whole-genome bisulfite sequencing (WGBS) and RNA sequencing, respectively. Between the two developmental stages, 1,250 of 3,379 differentially methylated regions (DMRs) were annotated in differentially methylated genes (DMGs), and these regions were mainly related to intercellular communication and the cytoskeleton. Integrated analysis of the methylome and transcriptome data led to the identification of 14 overlapping genes that encode crucial factors for wool fiber development through epigenetic mechanisms. Furthermore, a functional study using human hair inner root sheath cells (HHIRSCs) revealed that, one of the overlapping genes, platelet-derived growth factor C (PDGFC) had a significant effect on the messenger RNA expression of several key HF-related genes that promote cell migration and proliferation. Our study presents an unprecedented analysis that was used to explore the enigma of fleece morphological changes by combining methylome maps and transcriptional expression, and these data revealed stage-specific epigenetic changes that potentially affect fiber development. Furthermore, our functional study highlights a possible role for the overlapping gene PDGFC in HF cell growth, which may be a predictable biomarker for fur goat selection.

The Tibetan cashmere goat is one of the main goat breeds used by people living in the plateau. It exhibits the distinct phenotypic characteristics observed in lowland goats, allowing them to adapt to the challenging conditions at high altitudes. It provides an ideal model for understanding the genetic mechanisms underlying high-altitude adaptation and hypoxia-related diseases. Our previous exome sequencing of five Chinese cashmere breeds revealed a candidate gene, DSG3 (Desmoglein 3), responsible for the high-altitude adaptation of the Tibetan goat. However, the whole DSG3 gene (44 kbp) consisting of 16 exons in the goat genome was not entirely covered by the exome sequencing. In this study, we resequenced all the 16 exons of the DSG3 gene in ten Chinese native goat populations. Twenty-seven SNP variants were found between the lowland and highland goat populations. The genetic distance (FST) of significant SNPs between the lowland and highland populations ranged from 0.42 to 0.58. By using correlation coefficient analysis, linkage disequilibrium, and haplotype network construction, we found three non-synonymous SNPs (R597E, T595I, and G572S) in exon 5 and two synonymous SNPs in exons 8 and 16 in DSG3. These mutations significantly segregated high- and low-altitude goats in two clusters, indicating the contribution of DSG3 to the high-altitude hypoxia adaptation in the Tibetan goat.