The comprehensive assessment of epigenetics changes during skin development

Epigenetic regulation is critical to multiple physiological and pathological processes. However, little is known regarding the epigenetic changes during neonatal skin development and skin aging, and in response to ultraviolet (UV) exposure. The transcriptomes of human skin samples from different ages or irradiated with different types and doses of UV light were analyzed using R (version 4.0.3) software. The epigenetic landscape of the skin, including histone modifications, genetic imprinting and m⁶A modification, which are mainly involved in collagen formation, extracellular matrix organization, immune function and keratinization, underwent significant changes during neonatal to adult development. Epigenetic effectors such as IGF2BP2, GATA2, GATA3, CPA4 and CDK1 were significantly correlated with extracellular matrix organization, and VEGFA, CDK1 and PRKCB with skin immune function. The m⁶A readers such as IGF2BP2, IGF2BP3, HNRNPA2B1 and EIF3G showed significant correlation with extracellular matrix organization, metabolism, or antigen processing and presentation. Small doses of UV exposure only induced changes in the expression levels of some epigenetic effectors, without any significant effect on the overall epigenetic landscape. However, the minimal erythema dose of UV exposure altered multiple epigenetic effectors regulating extracellular matrix organization, cell-matrix adhesion, innate immune response, mitochondrial function and mRNA processing. In addition, epigenetic changes following UV exposure were more pronounced in the elderly skin compared to the younger skin. In conclusion, histone modifications, genetic imprinting and m⁶A modification play critical roles during skin development, and a large dose of UV exposure can significantly change the expression of multiple epigenetic effectors.