Coordinated activation of a cluster of MMP genes in response to UVB radiation
Coordinated activation of a cluster of MMP genes in response to UVB radiation
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DOI：
10.1038/s41598-018-20999-6
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发表时间：
2018-02-08
影响因子：
4.6
通讯作者：
Boros, Imre M.
中科院分区：
文献类型：
--
作者：
Ujfaludi, Zsuzsanna;Tuzesi, Agota;Boros, Imre M.
紫外线（UV） B辐射是一种危险的环境应激源，可导致光老化、炎症、免疫抑制和肿瘤形成。最近的一份报告显示，包括基质金属蛋白酶（MMPs）在内的几种皮肤特异性基因在紫外线照射下的转录激活。在这里，我们使用一种新的人类角质细胞模型HKerE6SFM来证明UVB激活了11q22.3 MMP基因簇的大多数成员的转录，包括MMP13、MMP12、MMP3、MMP1和MMP10。奇怪的是，uvb诱导的MMP9的表达保持不变，它位于簇外。与UVB照射后MMP基因簇的表达增加一致，RNA聚合酶II在UVB照射后其启动子处的占用率增加。结果还表明，在MMP13、MMP12、MMP3、MMP1和MMP10基因的启动子上乙酰化组蛋白H3K9水平升高。这些研究结果表明，在11q22.3位点，MMP基因簇中存在协调的转录激活，赖氨酸9位点组蛋白H3的乙酰化在uvb依赖性增强MMP基因在该区域的转录中起重要作用。
Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10. Curiously, the expression of the well-characterized UVB-inducible MMP9, which is located outside of the cluster, remains unchanged. In accordance with the increased expression of the MMP gene cluster upon UVB irradiation, RNA polymerase II showed increased occupancy at their promoters following UVB irradiation. The results also demonstrate increased acetylated histone H3K9 levels at the promoters of the MMP13, MMP12, MMP3, MMP1 and MMP10 genes. These findings suggest a coordinated transcriptional activation of genes in the MMP cluster at 11q22.3 and that acetylation of histone H3 at lysine 9 has an important role in the UVB-dependent enhancement of transcription of MMP genes in this region.