The maintenance of normal blood functionality is vital for the host organisms. It requires a complex array of regulatory elements to regulate the development and maturation of various haematopoietic linages. Unlike enhancers and promoters, the landscape of lineage-specific silencers and their regulatory output is still poorly understood. This project aims to integrate multi-omics data to characterise genome-wide candidate silencers in myeloid/lymphoid lineages, followed by high-throughput reporter screens and functional validation by CRISPR/CAS9 knockdown. We will develop a machine-learning algorithm to predict lineage-specific silencers based on sequence features, providing vital knowledge of the complex regulatory network in the blood system.
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