Sheep IGFBP2 and IGFBP4 promoter methylation regulates gene expression and hair follicle development

Abstract

Background: Hair follicle development is important for the fineness of wool. Our previous methylated DNA immunoprecipitation sequencing showed that IGFBP2 and IGFBP4 were differentially methylated at different development stages of the hair follicle of Super Merino sheep. This study selected these two genes as candidates to uncover the influence of their promoter methylation on hair follicle development.

Results: The results showed that the expression levels of IGFBP2 and IGFBP4 in the skin of very fine wool Super Merino sheep were higher than that in the very thick wool group, and the difference for IGFBP4 was significant. The total methylation rate of IGFBP2 promoter was extremely low, and no significant difference was found in the skin tissue of the Super Merino sheep at different fineness groups. However, the total methylation rate of IGFBP4 promoter in the very thick group was significantly higher than that in the very fine group, and the total DNA methylation levels of the IGFBP4 were significantly negatively correlated with mRNA expression. Furthermore, the transcription factor prediction results showed 104 and 91 candidate binding sites for transcription factors in the promoter regions of IGFBP2 and IGFBP4, respectively. Among these, JUN, EP300, SP1, PAX6, ETS1, and MYOD1 may be related to hair follicle development.

Conclusions: The total methylation level of IGFBP4 promoter was negatively correlated with its mRNA expression in Super Merino sheep skin tissues with different degrees of fineness, which could be used as an epigenetic marker for wool breeding in Super Merino sheep.