Research interests
Our work has demonstrated that the exchange of the core histone H2A with its variant forms, in particular the essential histone variant H2A.Z, represents one of the most profound and crucial epigenetic processes that is required for early metazoan development, chromosome organisation and inheritance, as well as regulating promoter chromatin architecture to maintain or change cell fate. Mechanistically, we demonstrated that H2A.Z, and other types of H2A variants, performs these crucial functions by directly regulating the extent of chromatin compaction. Recently, we have also found that histone H2A variants are located at intron-exon boundaries to regulate pre-mRNA splicing, which is critical for male fertility and brain function. Moreover, we have found that the mis-incorporation of histone H2A variants into chromatin plays an important role in the progression of cancer.
To further understand the role of the epigenome, including the role of histone variants, in regulating genome function, we have established long-range genome mapping and computational 3D genome modelling approaches, which revealed how active and inactive genes are packaged and segregated into different 3-dimensional compartments within a chromosome during the differentiation of human stem cells.