Plantar pain in pachyonychia congenita
Plantar pain in pachyonychia congenita
复制标题
先天性厚甲症的足底疼痛
DOI：
--
复制
发表时间：
2018
影响因子：
10.3
通讯作者：
E. O’Toole
中科院分区：
文献类型：
--
作者：
M. Krupiczojc;E. O’Toole
MMP 1表达，表明P300是MMP 1启动子处H3乙酰化所需的。在这一期的BJD中，Ding等人发现，在中年志愿者中，相对于受保护的部位，暴露于光的皮肤部位的H3乙酰化整体增加，包括MMP 1启动子处的H3乙酰化以及MMP 1和P300表达的增加。由于暴露部位与受保护部位的差异在年轻志愿者中并不明显，因此，随着时间的推移，皮肤的急性UVR表观遗传反应显示为更永久的特征。这项工作强调了光损伤皮肤中存在一种机制，该机制促进H3乙酰化超过MMP 1启动子的脱乙酰化，维持MMP 1过表达并促进胶原蛋白片段化。DNA损伤标记物c-H2 Ax（另一种组蛋白修饰）在MMP 1启动子处与P300相互作用，提示DNA损伤在诱导H3乙酰化中的直接作用。光损伤皮肤中未修复的DNA损伤会促进H3乙酰化而不是去乙酰化吗？H3乙酰化现在提供了一种途径来研究光损伤皮肤中的基因表达扰动，并帮助解开驱动胶原蛋白断裂的机制。Ding等人在老年光暴露皮肤中的308个基因启动子处鉴定出改变的H3乙酰化，整体H3乙酰化是光暴露皮肤的比H4乙酰化和H3 K4或H3 K9甲基化更显著的特征。然而，在确定H3乙酰化是光损伤皮肤中主要的表观遗传变化之前，需要与其他组蛋白修饰和DNA甲基化进行直接比较。此外，需要鉴定驱动胶原降解的基因网络，以评估MMP 1表观遗传变化对胶原断裂的相对重要性。尽管如此，H3的乙酰化可能是光损伤皮肤中几百个基因表达扰动的管道，包括关键的胶原降解酶MMP 1。
MMP1 expression, demonstrating that P300 was required for H3 acetylation at the MMP1 promoter. In this issue of the BJD, Ding et al. find global increases in H3 acetylation, in a photo-exposed skin site relative to a protected site in middleaged volunteers, including H3 acetylation at the MMP1 promoter and increases in MMP1 and P300 expression. As the exposed-to-protected site differences were not evident in younger volunteers, skin’s acute UVR epigenetic response was therefore shown to become a more permanent feature over time. This work highlights the existence of a mechanism in photodamaged skin that promotes H3 acetylation over deacetylation at the MMP1 promoter, maintaining MMP1 overexpression and contributing to collagen fragmentation. The DNA damage marker c-H2Ax (another histone modification) interacts with P300 at the MMP1 promoter, suggestive of a direct role for DNA damage in the induction of H3 acetylation. Could unrepaired DNA damage in photodamaged skin be promoting H3 acetylation over deacetylation? H3 acetylation now offers a route to investigate gene expression perturbations in photodamaged skin and help unravel the mechanisms driving collagen fragmentation. Altered H3 acetylation was identified at 308 gene promoters in older photo-exposed skin by Ding et al., and global H3 acetylation was a more prominent feature of photo-exposed skin than H4 acetylation and H3K4 or H3K9 methylation. However, direct comparisons with other histone modifications and DNA methylation are needed before H3 acetylation is determined as the major epigenetic change in photodamaged skin. In addition, identification of the gene network driving collagen degradation is required to assess the relative importance of MMP1 epigenetic changes to collagen fragmentation. Nonetheless, acetylation of H3 is likely a conduit for a few hundred gene expression perturbations in photodamaged skin, including the key collagen degradation enzyme MMP1.
影响因子：
6.5
作者：
Fligiel, SEG;Varani, J;Voorhees, JJ
通讯作者：
Voorhees, JJ
影响因子：
12.4
作者：
Leachman, Sancy A.;Hickerson, Robyn P.;Kaspar, Roger L.
通讯作者：
Kaspar, Roger L.
影响因子：
15.9
作者：
Kerns, Michelle L.;Hakim, Jill M. C.;Coulombe, Pierre A.
通讯作者：
Coulombe, Pierre A.