Chromatin and epigenetic landscape of differentiating CD34 haematopoietic cells and the impact of viral infection

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Haematopoiesis is an essential process that underpins the normal development of ourimmune system. CD34+ progenitor cells resident in the bone marrow are committed todifferent cell fates through mechanisms that are not completely understood but arehypothesized to involve dynamic regulation of gene expression through short and long rangeepigenetic interactions. CD34+ progenitor cells are an important site for humancytomegalovirus (HCMV) lifelong latent infections in the host. Intriguingly, HCMV ispreferentially detected in differentiated myeloid cells suggesting that the virus activelyregulates cell fate.Our aim is to understand how does the chromatin and epigenetics landscapes change duringthe latent infection and to identify potential signatures crucial for myeloid cell commitment.To do this, we will use fluorescently tag expressing viruses to sort infected cells and culturethem for seven days to compare them with uninfected and bystander cells from the infection.This work will be done in the Reeves lab (the secondary supervisor) that has extensiveexpertise with HCMV, particularly studies of viral latency in CD34+ cells, and access to stateof-the-art sorting facilities at UCL. Once isolated, we will perform ChIP-seq to investigatedistribution of epigenetic marks (H3K27ac, H3K4me1 and H3K4me3) and of the architecturalproteins (CTCF and Cohesin) on the human genome and HiChIP to investigate the 3D wiringof the DNA under the different experimental conditions. We will also extract the RNA andsequence the libraries to detect changes in gene expression. This work will be done in Zabetlab (primary supervisor) that has extensive expertise in chromatin and epigenetics bothwetlab and computational.