MacDonald Ian A, Hathaway Nathaniel A
Division of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
1] Division of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Immunol Cell Biol. 2015 Mar;93(3):261-70. doi: 10.1038/icb.2014.105. Epub 2014 Dec 23.
The ability to accurately quantitate and experimentally examine epigenetic modifications across the human genome has exploded in the past decade. This has given rise to a wealth of new information concerning the contributions of epigenetic regulatory networks to the pathogenesis of human disease. In particular, immunological disorders have strong developmental roots in chromatin regulatory pathways. In this review, we focus on the epigenetic signatures and new discoveries revealing the epigenetic compositions of specific immunological cancers and autoimmune diseases. We also comment on the conserved epigenetic roots among diverse immunological disorders and suggest inhibition strategies that may be relevant for future treatment. Finally, we highlight emerging experimental tools with the capability to examine the mechanisms of chromatin regulatory enzymes with a high level of temporal control. The knowledge of genetic and epigenetic defects in immunological disease combined with new experimental approaches will elucidate the contribution of individual enzymes in complex epigenetic regulatory networks. This could lead to new diagnostic and therapeutic approaches for some very diverse and difficult to treat human diseases.
在过去十年中,准确量化和实验检测人类基因组表观遗传修饰的能力得到了极大的发展。这催生了大量关于表观遗传调控网络对人类疾病发病机制贡献的新信息。特别是,免疫紊乱在染色质调控途径中有着很强的发育根源。在这篇综述中,我们聚焦于表观遗传特征以及揭示特定免疫性癌症和自身免疫性疾病表观遗传组成的新发现。我们还评论了不同免疫紊乱之间保守的表观遗传根源,并提出可能与未来治疗相关的抑制策略。最后,我们重点介绍了新兴的实验工具,这些工具能够在高度的时间控制下检测染色质调控酶的机制。免疫性疾病中遗传和表观遗传缺陷的知识与新的实验方法相结合,将阐明个体酶在复杂表观遗传调控网络中的作用。这可能会为一些非常多样且难以治疗的人类疾病带来新的诊断和治疗方法。