端粒异染色质形成的分子基础

异染色质结构的建立和维持是真核生物最典型、最保守的表观遗传现象。过去几十年的研究已经鉴定出大量维持异染色质结构所需的顺式元件和反式因子。但由于技术上的困难，异染色质的建立过程及其分子机理至今没有得到很好的阐释。我们以酿酒酵母端粒异染色质为模型，建立了一个可以模拟DNA复制后异染色质起始性形成的系统。通过精细的遗传改造，该系统能够实现异染色质建立过程中各个环节的可视化和可控化，并能够让我们准确地测定异染色质建立过程中相关顺式元件和反式因子的相互作用及动态变化。我们将利用该系统，结合遗传、生化及细胞学手段来深入地阐述酿酒酵母异染色质形成的动态过程、分子机制和生理意义。

The establishment and maintenance of heterochromatin is one of the most conserved epigenetic inheritances in eukaryotes. In the past decades, dozens of genes have been shown to regulate heterochromatin structure in-cis and in-trans. However, duo to the technical difficulties, the molecular mechanism of heterochromatin assembly and maintenance still remains elusive. In this proposal, we will use budding yeast S. cerevisiae telomeres to study the molecular events involved in the process of telomere heterochromatin formation. We have set up a de novo telomere addition system which allows us to manipulate and visualize almost every step of telomere heterochromatin assembly, and to determine the genetic and epigenetic requirements for heterochromatin formation. By exploiting this system in combination with genetic, biochemical and cell biology approaches, we anticipate to dissect the dynamics and molecular mechanism of heterochromatin formation, and to explore the physiological significance of heterochromatin.