Understanding how the NuRD complex functions in mouse embryonic stem cells (mESC's)

胚胎干细胞（ES）具有多能性；它们既可以自我更新，也可以分化成人体的任何一种特化细胞类型。多能性是由一组核心转录因子维持的，这些转录因子是与基因调控区域结合并促进其表达的蛋白质。核小体重塑和去乙酰化酶（NuRD）复合物在控制转录因子结合以使胚胎干细胞分化方面起着核心作用。该项目将使用一种被称为3D单分子成像的超分辨率显微镜来研究NuRD如何控制转录调节因子在其靶基因上的结合。这些调节因子结合在增强子区域，即基因附近的DNA片段，通常需要与基因的其他部分靠近才能进行转录，但其机制尚不完全清楚。因此，该项目还旨在研究NuRD如何调节增强子与其同源基因的接近程度，并直接可视化这对这些基因转录动力学的影响。

Embryonic stem (ES) cells are pluripotent; they can either self-renew or differentiate into any of the body's specialised cell types. Pluripotency is maintained by a core set of transcription factors-proteins that bind to regulatory regions of genes and promote their expression. The Nucleosome Remodelling and Deacetylase (NuRD) complex plays a central role in controlling transcription factor binding to allow ES cells to differentiate. This project will use a form of super-resolution microscopy known as 3D single-molecule imaging to investigate how NuRD controls the binding of transcriptional regulators at their target genes. These regulators bind at enhancer regions, stretches of DNA near a gene that often need to be brought into proximity with the rest of a gene to enable transcription-but the mechanism is not fully understood. This project will therefore also aim to study how NuRD regulates the proximity of enhancers to their cognate genes and directly visualise the effect this has on the kinetics of transcription at those genes.