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

Haematopoiesis is an essential process that underpins the normal development of our
immune system. CD34+ progenitor cells resident in the bone marrow are committed to
different cell fates through mechanisms that are not completely understood but are
hypothesized to involve dynamic regulation of gene expression through short and long range
epigenetic interactions. CD34+ progenitor cells are an important site for human
cytomegalovirus (HCMV) lifelong latent infections in the host. Intriguingly, HCMV is
preferentially detected in differentiated myeloid cells suggesting that the virus actively
regulates cell fate.
Our aim is to understand how does the chromatin and epigenetics landscapes change during
the 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 culture
them 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 extensive
expertise 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 investigate
distribution of epigenetic marks (H3K27ac, H3K4me1 and H3K4me3) and of the architectural
proteins (CTCF and Cohesin) on the human genome and HiChIP to investigate the 3D wiring
of the DNA under the different experimental conditions. We will also extract the RNA and
sequence the libraries to detect changes in gene expression. This work will be done in Zabet
lab (primary supervisor) that has extensive expertise in chromatin and epigenetics both
wetlab and computational.