通过基因组书签塑造表观遗传记忆
Shaping Epigenetic Memory via Genomic Bookmarking
摘要：
通过组蛋白修饰的快速周转及其对外部刺激的适应性来验证表观遗传模式的稳定性是一个突出的挑战。在这里，我们提出了一种新的生物物理机制，可以通过基因组书签（GBM）建立和维持强大而可塑的表观遗传结构域。我们将染色质建模为一个非永久性的聚合物，其片段带有非永久性的组蛋白标记（或颜色），可以被“作家”蛋白质修饰。三维染色质组织由蛋白质桥或“阅读器”介导，例如多梳抑制复合物和转录因子。读者和作者之间的耦合驱动生化标记的传播，并在复制和有丝分裂中维持局部染色质状态的记忆。相反，GBM靶向扰动使表观遗传模式不稳定。引人注目的是，我们证明，GBM单独可以解释整个果蝇染色体的Polycomb标记的全部分布。最后，我们建议，我们的模型提供了一个起点，了解细胞分化和重编程的生物物理学。
英文摘要：
Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by "writer" proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or "readers", such as Polycomb Repressive Complexes and Transcription Factors. The coupling between readers and writers drives spreading of biochemical marks and sustains the memory of local chromatin states across replication and mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. We finally suggest that our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
