Whole-genome bisulfite sequencing of goat skins identifies signatures associated with hair cycling

Abstract

Hair follicles (HFs), upon development, undergo repetitive cycles of growth (anagen), regression (catagen), and rest (telogen). The transition between the stages is determined by multiple molecular signals, including DNA methylation, which plays important roles in mammalian cellular identity and is essential for the development of HFs. Secondary hair follicles (SHFs) in cashmere goat exhibit classic cyclic hair development, and little has been done on a genome-wide scale to examine potentially methylated genes involved in the hair cyclic transition. Genome-wide DNA methylation profiles between skin tissues sampled during the anagen and telogen stages in cashmere goats were investigated using whole-genome bisulfite sequencing (WGBS). The methylation status was observed to be higher in the skin samples with HFs in the telogen than those in the anagen stage. A total of 1311 differentially methylated regions (DMRs) were identified between the two groups, which contained 493 fully annotated DMR-related genes (DMGs) (269 Hyper- DMGs and 224 Hypo-DMGs). Furthermore, a significant over-representation of the functional categories for DMGs related to immune response and intercellular crosstalk during hair cycling was observed. By integrating DNA methylation and mRNA expression data, we revealed that four genes (FMN1, PCOLCE, SPTLC3, and COL5A1) are crucial factors for elucidating epigenetic mechanisms contributing to the telogen-to-anagen transition. Our study provided systematic methylome maps pertaining to the hair cycling stages (anagen vs telogen) at a single-base resolution, and revealed stage-specific methylation loci during cashmere growth or quiescence. Furthermore, we identified epigenetically regulated genes that are potentially involved in HF development and growth in cashmere goats, and likely in other mammal species.