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慢性阳光暴露与人皮肤中独特的组蛋白乙酰化变化有关。

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

机构信息

Department of Dermatology, The Third Xiangya Hospital of Central South University, 138 Tong Zipo Road, Changsha, 410013, Hunan, China.

出版信息

Br J Dermatol. 2018 Jul;179(1):110-117. doi: 10.1111/bjd.16129. Epub 2018 May 27.

Abstract

BACKGROUND

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

OBJECTIVES

To analyse histone modification patterns in sun-exposed and nonexposed skin, and to identify the abnormally histone-modified genes related to photoageing.

METHODS

Skin biopsies were collected from both 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 enzyme-linked immunosorbent assay. Expression levels of histone acetyltransferases and histone deacetylases were measured by reverse-transcriptase quantitative polymerase chain reaction (qPCR) and Western blot. Chromatin immunoprecipitation combined with DNA microarray (ChIP-chip) assay with anti-acetyl-histone H3 antibody in a sun-exposed pool (combining six sun-exposed skin samples) and a nonexposed pool (combining six nonexposed skin samples) was conducted to explore the abnormally acetylated histone H3 genes related to photoageing; ChIP-qPCR was then used to verify the results of ChIP-chip.

RESULTS

We observed higher global histone H3 acetylation levels increased EP300 and decreased HDAC1 and SIRT1 expression in sun-exposed skin compared with matched nonexposed skin. Furthermore, the ChIP-chip assay 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 acetylation 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 photoageing.

摘要

背景

光老化归因于持续的阳光或人工紫外线暴露,表现为皮肤的临床和组织学变化。已发现表观遗传变化参与光老化的发病机制。然而,潜在机制尚不清楚。

目的

分析暴露于阳光和未暴露于阳光的皮肤中的组蛋白修饰模式,并确定与光老化相关的异常组蛋白修饰基因。

方法

从 20 名健康中年女性志愿者的前臂外侧(暴露于阳光的区域)和臀部(暴露于阳光的区域)采集皮肤活检。通过酶联免疫吸附试验评估全局组蛋白 H3/H4 乙酰化和 H3K4/H3K9 甲基化状态。通过逆转录定量聚合酶链反应(qPCR)和 Western blot 测量组蛋白乙酰转移酶和组蛋白去乙酰化酶的表达水平。用抗乙酰化组蛋白 H3 抗体进行暴露于阳光的池(合并六个暴露于阳光的皮肤样本)和未暴露于阳光的池(合并六个未暴露于阳光的皮肤样本)的染色质免疫沉淀结合 DNA 微阵列(ChIP-chip)测定,以探讨与光老化相关的异常乙酰化组蛋白 H3 基因;然后使用 ChIP-qPCR 验证 ChIP-chip 的结果。

结果

与匹配的未暴露皮肤相比,我们观察到暴露于阳光的皮肤中组蛋白 H3 乙酰化水平升高,EP300 增加,HDAC1 和 SIRT1 表达减少。此外,ChIP-chip 测定显示,两组之间有 227 个基因显示出组蛋白 H3 的显著过度乙酰化,有 81 个基因显示出组蛋白 H3 的显著低乙酰化。PDCD5、ITIH5、MMP1 和 AHR 基因启动子上的组蛋白 H3 乙酰化水平与相应基因的 mRNA 表达呈正相关。

结论

慢性阳光暴露诱导的组蛋白 H3 过度乙酰化可能在皮肤光老化的发病机制中起关键作用。

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