Research Groups > Gene Regulation and Chromatin

A major aim of our research is to identify the epigenetic mechanisms that are responsible for stem cell plasticity and to understand the role played by epigenetic effects in generating specific patterns of gene expression during cell differentiation. Our studies are focused in particular on the role played by sequence-specific transcription factors in establishing complex epigenetic marks at tissue-specific genes in embryonic stem cells and maintaining or altering these marks as cells differentiate.

During the later stages of cell differentiation, cells generally exit the cell cycle and become specialized for different functions. We are studying how this process occurs in antibody-producing plasma cells and how combinatorial histone modifications are used to silence large regions of the genome and package them into heterochromatin as the cells specialize to become antibody factories. Transformation of plasma cells gives rise to multiple myeloma, a common cancer which develops in the bone marrow and causes bone fractures and kidney failure. We are investigating how the normal process of programmed cell death in plasma cells is subverted in multiple myeloma and how this information can be used to devise strategies for treating the disease.

Figure 1. The Aurora B kinase (green) is tightly localised to the spindle In a dividing telophase plasmablast. A different distribution is observed in fully differentiated plasma cells, which have exited the cell cycle. In these cells, Aurora B is more widely distributed in the nucleus, with the highest concentrations observed around the dense regions of facultative heterochromatin (grey DAPI staining).
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Figure 2. Distribution of the double histone H3 tri-methyl lysine 9 / phospho-serine10 modification across a gene-dense region of mouse chromosome 3. The ChIP-on-chip analysis was carried out on undifferentiated cells from a mesenchymal stem cell line and cells that had been induced to differentiate into osteocytes. Silent genes (yellow) are specifically enriched for the double modification in differentiated cells, whereas active genes are depleted for the modification.
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