UNDERSTANDING THE INTERPLAY OF ENHANCERS, CHROMATIN PRIMING ELEMENTS AND SIGNALS REGULATING DYNAMIC GENE EXPRESSION IN DEVELOPMENT

在胚胎发育过程中，一个功能齐全的生物体的形成主要是由细胞外信号调节因子和基因表达调节因子协调和控制的。胚胎发育的一个令人着迷的方面是，不同细胞形成的时间总是相同的。这种同步的原因是，我们身体计划的所有信息都编码在我们的DNA中，DNA包含关于我们的基因何时应该表达，何时应该沉默的指令。此外，发育中的细胞通过信号进行交流，以同步它们的发育，并激活基因来产生蛋白质，这种蛋白质被称为转录因子，可以“读取”遗传密码。这些因子与许多其他蛋白质一起工作，以确保基因在正确的细胞和正确的时间表达。然而，我们的DNA被包装成一种称为染色质的紧密结构，一方面确保它适合细胞核，但另一方面限制转录因子的进入。染色质结构、转录因子和信号如何共同调节基因表达尚不清楚。为了回答这个问题，我们将使用一种模拟体外正常发育的体外分化系统。我们将收集所有基因的数据，我们将使用计算生物学方法来回答在发育过程中如何控制基因表达的平衡和时间这一基本问题。

The formation of a fully functional organism during embryonic development is primarily coordinated and controlled by extra-cellular signalling modulators and regulators of gene expression. A fascinating aspect of embryonic development is that the timing of how different cells form is always the same. The reason for this synchrony is that all information for our body plan is encoded in our DNA, which contains instructions on when our genes should be expressed and when they should be silent. Moreover, developing cells communicate via signals to synchronize their development and activate genes to produce proteins, called transcription factors which can "read" the genetic code. These factors work together with many other proteins to ensure that genes are expressed in the right cell and at the right time. However, our DNA is packaged into a compact structure called chromatin which on the one hand ensures that it fits into the nucleus, but on the other hand restricts transcription factor access. How chromatin structure, transcription factors and signals work together to properly regulate gene expression is unclear. To answer this question, we will use an in vitro differentiation system that mimics normal development in vitro. We will collect data on all genes, and we will use computational biology methods to answer the fundamental question of how the balance and timing of gene expression are controlled in development.