PDF(Pubmed)
Abstract：
Epigenetic mechanisms enable cells to develop novel adaptive phenotypes without altering their genetic blueprint. Recent studies show histone modifications, such as heterochromatin-defining H3K9 methylation (H3K9me), can be redistributed to establish adaptive phenotypes. We developed a precision-engineered genetic approach to trigger heterochromatin misregulation on-demand in fission yeast. This enabled us to trace genome-scale RNA and H3K9me changes over time in long-term, continuous cultures. Adaptive H3K9me establishes over remarkably slow timescales relative to the initiating stress. We captured dynamic H3K9me redistribution events which depend on an RNA binding complex MTREC, ultimately leading to cells converging on an optimal adaptive solution. Upon stress removal, cells relax to new transcriptional and chromatin states, establishing memory that is tunable and primed for future adaptive epigenetic responses. Collectively, we identify the slow kinetics of epigenetic adaptation that allow cells to discover and heritably encode novel adaptive solutions, with implications for drug resistance and response to infection.
摘要：
表观遗传机制使细胞能够开发新的适应性表型而不改变其遗传蓝图。最近的研究表明组蛋白修饰，如异染色质定义H3K9甲基化(H3K9me)，可以重新分配以建立适应性表型。我们开发了一种精确工程的遗传方法来触发裂变酵母中按需的异染色质失调。这使我们能够长期追踪基因组规模的RNA和H3K9me随时间的变化，持续的文化。自适应H3K9me相对于起始压力在非常慢的时间尺度上建立。我们捕获了依赖于RNA结合复合物MTREC的动态H3K9me再分布事件，最终导致细胞聚集在一个最佳的自适应解决方案上。消除应力后，细胞放松到新的转录和染色质状态，建立可调节的记忆，为未来的适应性表观遗传反应做好准备。总的来说，我们确定了表观遗传适应的缓慢动力学，允许细胞发现并遗传编码新的适应性解决方案，影响耐药性和对感染的反应。
