Histone exchange chromatin dynamics and chromatin function: Role of ATP-dependent chromatin remodelling factor Fun30 in epigenetics

每个细胞中的遗传物质都是由一种极其复杂的异质结构包装和组织起来的，称为染色质。这种结构的基本构件是核小体，这是一个分子蛋白质卷轴，DNA几乎绕着它绕两圈。核小体被修饰，并与其他蛋白质相互作用，产生染色质结构，从而关闭基因或允许进入从基因读出信息的机器。特定的染色质结构介导基因调节，是基因组稳定和染色体分离所必需的。这样的结构必须被忠实地复制，以在发育过程中维持基因表达模式。异染色质的缺陷被认为与基因组不稳定、不孕不育、加速衰老和癌症风险增加有关。尽管有这种基本的重要性，但我们对特定的染色质结构，如异染色质，是如何组装和维持的知识是有限的。我们将研究核小体重塑和修饰酶如何相互作用，以组装特定的染色质结构，关闭基因，稳定基因组。这项研究不仅对我们理解正常发育有意义，而且对癌症和生育也有影响。

The genetic material in each cell is packaged and organized by an extremely complex, heterogeneous structure, called chromatin. The basic building block of this structure is the nucleosome, a molecular protein spool around which DNA winds in almost two turns. Nucleosomes are modified and interact with other proteins to create chromatin structures that shut down genes or allow access to the machinery that read out the information from genes. Specific chromatin structures mediate gene regulation and are required for genome stability and chromosome segregation. Such structures have to be faithfully duplicated for the maintenance of gene expression patterns through development. Defects in heterochromatin have been linked to genome instability, infertility, accelerated aging and an enhanced risk of cancer. Despite this fundamental importance, our knowledge of how specific chromatin structures, such as heterochromatin, are assembled and maintained is limited. We will study how nucleosome remodelling and modification enzymes interact to assemble a specific chromatin structure to shut down genes and to stabilise the genome. This research has implications for our understanding of normal development, but also for cancer and fertility.