Chronic sun exposure is associated with distinct histone acetylation changes in human skin

Abstract

Background

Photoaging is attributed to continuous sunlight or artificial UV exposure and manifests the clinical and histological changes of skin. Epigenetic changes have been found to be involved in the pathogenesis of photoaging. However, the underlying mechanisms are unclear.

Objectives

To analyse histone modification patterns in sun-exposed and non-exposed skins, and identify the abnormally histone modified-genes related to photoaging.

Methods

Skin biopsies were collected both from the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers. Global histone H3/H4 acetylation and H3K4/H3K9 methylation statuses were assessed by ELISA. Expression levels of HATs and HDACs were measured by RT-qPCR and western blot. ChIP-chip assay with anti-acetyl-histone H3 antibody in sun-exposed Pool (combining six sun-exposed skin samples) and non-exposed Pool (combining six non-exposed skin samples) was conducted to explore the abnormal histone H3 acetylation genes related to photoaging, then ChIP-qPCR was followed to verify the results of ChIP-chip.

Results

We observed higher global histone H3 acetylation level, increased P300 and decreased HDAC1 and SIRT1 expression in sun-exposed skins, compared with matched non-exposed skins. Further, ChIP-chip assay results showed that 227 genes displayed significant hyperacetylation of histone H3, and 81 genes displayed significant hypoacetylation of histone H3 between the two groups. Histone H3 acetylations levels on the promoters of PDCD5, ITIH5, MMP1 and AHR were positively correlated with the mRNA expression of the corresponding gene.

Conclusions

Chronic sun exposure induced histone H3 hyperacetylation may play a critical role in the pathogenesis of skin photoaging.

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