Cancer is often caused by dysregulated expression of oncogenes or tumour suppressor genes. Post-translational modifications of histone proteins is one of the fundamental mechanisms that regulates gene expression.
In the context of the human genome, DNA is complexed with histone proteins to form nucleosomes and chromatin (Figure 1). This functional organization of the genome is tightly regulated to ensure the appropriate gene expression patterns.
Active genes are located in euchromatin. Euchromatin has an open structure, which allows transcription factors to bind the promoters of these genes. Conversely, inactive genes are sequestered into compact structures called heterochromatin where they are silenced.
Disruption of this balance between euchromatin and heterochromatin can have disastrous effects on normal cell functions, and can lead to unrestricted cell growth, resulting in the development of cancer.
Our lab utilizes a combination of molecular biology and biochemistry techniques to dissect the mechanisms of how histones and histone modifications regulate gene functions.
We have two main questions:
To address how signal transduction pathways converge onto histones to regulate gene expression we are are studying the role of H3 phosphorylation in the activation of immediate-early genes in mammalian cells.
To study the role of histone variants in the epigenetic regulation of gene expression, we are studying the H2A variant, H2A.Z.