Integrative Analysis of Methylation and Transcriptional Profiles to Reveal the Genetic Stability of Cashmere Traits in the Tβ4 Overexpression of Cashmere Goats

SIMPLE SUMMARY: Cashmere goats have double coats consisting of non-medullated fine inner hairs or cashmere fibers produced by secondary hair follicles (SHFs) and guard hairs produced by primary hair follicles (PHFs). Cashmere is an important economic product worldwide and the world market for cashmere is increasing while the current production of cashmere is limited. Thymosin β4 (Tβ4), a 4.9-kDa protein, contains 43 amino acids. Here, we produced Tβ4 overexpression (Tβ4-OE) offspring using two methods. The somatic cell nuclear transfer (SCNT) goats had increased hair follicle development and higher cashmere yields than wild type (WT) and natural mating (NM) goats. Taken together, our results showed that DNA methylation affected the expression of differentially expressed genes (DEGs) between generations and the genetic stability of cashmere traits. ABSTRACT: DNA methylation alteration is frequently observed in exogenous gene silencing and may play important roles in the genetic stability of traits. Cashmere is derived from the secondary hair follicles (SHFs) of cashmere goats, which are morphogenetically distinct from primary hair follicles (PHFs). Here, in light of having initially produced 15 Tβ4 overexpression (Tβ4-OE) cashmere goats which had more SHFs than the wild type (WT) goats, and produced more cashmere, we produced Tβ4-OE offsprings both via somatic cell nuclear transfer (SCNT) and via natural mating (NM). However, the desired trait exhibited lower fixation in the line-bred offspring compared to the SCNT offspring. Integrative analysis of methylation and transcriptional profiles showed that this might be due to the influence of methylation on the expression of differentially expressed genes (DEGs) between generations, which was mutually consistent with the results of the functional and pathway enrichment analysis of differentially methylated regions (DMRs) and DEGs. Overall, our study systematically describes the DNA methylation characteristics between generations of cashmere goats and provides a basis for improving genetic stability.