Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Trends Genet. 2019 Sep;35(9):645-657. doi: 10.1016/j.tig.2019.06.004. Epub 2019 Jul 10.
Epigenetic regulation is critical for the precise control of cellular fate and developmental programs. Disruption of epigenetic information is increasingly appreciated as a potential driving mechanism in both developmental disorders as well as ubiquitous diseases such as cancer. Consistent with this, mutations in histone modifying enzymes are amongst the most frequent events in all of human cancer. While early studies have focused on the canonical enzymatic functions involved in catalyzing modifications to histones, more recent studies have uncovered a new layer of critical nonenzymatic roles in transcriptional regulation for these proteins. Here, we provide an overview of these surprising, yet exciting, noncanonical, noncatalytic roles, and highlight how these revelations may have important implications for understanding disease and the future of epigenome-targeting therapies.
表观遗传调控对于细胞命运和发育程序的精确控制至关重要。越来越多的人认识到，表观遗传信息的破坏是发育障碍以及癌症等普遍疾病的潜在驱动机制。与此一致的是，组蛋白修饰酶的突变是人类癌症中最常见的事件之一。虽然早期的研究集中在催化组蛋白修饰的经典酶学功能上，但最近的研究揭示了这些蛋白质在转录调控中具有新的关键非酶学作用。在这里，我们概述了这些令人惊讶但又令人兴奋的非经典、非催化作用，并强调了这些发现可能对理解疾病和表观基因组靶向治疗的未来具有重要意义。
