Dissecting structural and functional cooperation between cis-regulatory elements in higher-order chromatin structures
The establishment of precise gene expression patterns during the development of multi-cellular organisms is controlled by the cisregulatory elements of the genome, which include gene promoters, enhancers, and boundary elements. In mammals, these elements can be separated by large genomic distances. To activate gene expression, spatial proximity between gene promoters and enhancers is facilitated within 3D genome structures, whose formation is dependent on the boundary elements. Many mammalian genes are controlled by multiple enhancers. However, it is not clear how these elements structurally and functionally cooperate with other cisregulatory elements to regulate gene expression. The aim of this project is to investigate when and how 3D genome structures form during cellular differentiation, how multiple cis-regulatory elements interact within these structures, and how this relates to gene activity levels. To achieve this, we will make use of a Chromosome Conformation Capture-based approach (“Tri-C”), which we have previously developed to enable high-resolution analysis of spatial interactions formed between multiple cis-regulatory elements in genomic regions of interest. Using this approach, we will examine the formation of 3D genome structures during cellular differentiation with high throughput. Furthermore, we will genetically delete enhancers and boundary elements in representative 3D structures and examine their functional interplay in the regulation of gene expression and the formation of genome structures. We anticipate that the proposed large-scale analysis of structural and functional properties of cisregulatory elements at high spatio-temporal resolution will contribute to our understanding of the complex relationship between genome structure and function.
Dr. A. Marieke Oudelaar,Göttingen
Max-Planck-Institut für Multidisziplinäre Naturwissenschaften
Am Fassberg 11