Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA, USA.
Methods Mol Biol. 2024;2842:103-127. doi: 10.1007/978-1-0716-4051-7_5.
Epigenome editing applications are gaining broader use for targeted transcriptional control as more enzymes with diverse chromatin-modifying functions are being incorporated into fusion proteins. Development of these fusion proteins, called epigenome editors, has outpaced the study of proteins that interact with edited chromatin. One type of protein that acts downstream of chromatin editing is the reader-effector, which bridges epigenetic marks with biological effects like gene regulation. As the name suggests, a reader-effector protein is generally composed of a reader domain and an effector domain. Reader domains directly bind epigenetic marks, while effector domains often recruit protein complexes that mediate transcription, chromatin remodeling, and DNA repair. In this chapter, we discuss the role of reader-effectors in driving the outputs of epigenome editing and highlight instances where abnormal and context-specific reader-effectors might impair the effects of epigenome editing. Lastly, we discuss how engineered reader-effectors may complement the epigenome editing toolbox to achieve robust and reliable gene regulation.
表观基因组编辑应用因其在靶向转录控制方面的广泛应用而受到越来越多的关注，因为越来越多具有不同染色质修饰功能的酶被整合到融合蛋白中。这些融合蛋白被称为表观基因组编辑器，其发展速度超过了与编辑染色质相互作用的蛋白质的研究。一类在染色质编辑下游起作用的蛋白质是读效器，它将表观遗传标记与基因调控等生物学效应联系起来。顾名思义，读效器蛋白通常由一个读域和一个效域组成。读域直接结合表观遗传标记，而效域通常募集介导转录、染色质重塑和 DNA 修复的蛋白复合物。在本章中，我们讨论了读效器在驱动表观基因组编辑结果中的作用，并强调了异常和特定于上下文的读效器可能会损害表观基因组编辑效果的情况。最后，我们讨论了如何利用工程化的读效器来补充表观基因组编辑工具箱，以实现稳健可靠的基因调控。
