Abstract:
We propose that several chromatin-mediated regulatory processes are dominated by source-sink relationships in which factors operate as \'sources\' to produce or provide a resource and compete with each other to occupy separate \'sinks\'. In this model, large portions of genomic DNA operate as \'sinks\', which are filled by \'sources\', such as available histone variants, covalent modifications to histones, the readers of these modifications and non-coding RNAs. Competing occupation for the sinks by different sources leads to distinct states of genomic equilibrium in differentiated cells. During dynamic developmental events, such as sexual reproduction, we propose that dramatic and rapid reconfiguration of source-sink relationships modifies chromatin states. We envision that re-routing of sources could occur by altering the dimensions of the sink, by reconfiguration of existing sink occupation or by varying the size of the source, providing a central mechanism to explain a plethora of epigenetic phenomena, which contribute to phenotypic variegation, zygotic genome activation and nucleolar dominance.
摘要:
我们建议,几种染色质介导的调节过程由源-汇关系主导,其中因子作为“源”来产生或提供资源,并相互竞争以占据单独的“汇”。在这个模型中,基因组DNA的大部分作为“汇”运行,由\'源\'填充,例如可用的组蛋白变体,共价修饰组蛋白,这些修饰和非编码RNA的读者。不同来源对汇的竞争占用导致分化细胞中基因组平衡的不同状态。在动态发育事件中,比如有性生殖,我们建议源-汇关系的戏剧性和快速重新配置会改变染色质状态。我们设想,通过改变水槽的尺寸,可以发生源的重新路由,通过重新配置现有的汇占用或通过改变源的大小,提供了一个解释大量表观遗传现象的中心机制,这有助于表型多样化,合子基因组激活和核仁优势。