Integrated genome-wide characterisation of silencer elements and their regulatory output in haematopoietic lineages

Dr Jun Wang (primary)
Barts Cancer Institute
Queen Mary University of London
Prof Eric So (secondary)
Department of Haematological Medicine
King’s College London

Abstract

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.


References

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3 Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature 2015 518, pages317–330.
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5 Cheung N, Fung,TK, Zeisig BB, Holmes K, Rane JK, Mowen KA, Finn MG, Lenhard B, Chan LC, *So CW. Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia. Cancer Cell. 29 (1): 32-48, 2016


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyGeneticsImmunology
Techniques & Approaches
BioinformaticsGeneticsMathematics / StatisticsMolecular BiologySimulation / Modelling