Decoding Transcription Factor Complexes in Cell Identity

Transcription factors (TFs) are key proteins that regulate gene expression by binding to specific regions of the genome known as regulatory elements (REs) such as promoters and enhancers. TFs do not act alone but interact with a wide range of other proteins and RNAs to determine which genes are active in a particular cell type. These interactions are highly context-specific and enable cells to establish and maintain their identity and their disruption can cause cells to change identity. For example, during human development, signals such as cytokines activate specific TFs that drive the formation of different tissues from stem and progenitor cells. In disease contexts, including cancer, changes in TF activity or the accessibility of REs can lead to abnormal gene expression and the emergence of pathological cell states. While recent advances in epigenomics have mapped many of the REs used across various cell types and developmental stages, the molecules including proteins and RNAs that act at these sites to control gene expression and define cell identity remain largely unknown. This is mainly due to the lack of tools capable of dissecting the composition and function of individual regulatory regions. Importantly, our group has developed and adopted several innovative epigenetic techniques that enable the characterisation of mammalian protein complexes at single locus resolution. In this project, these tools will be used to define transcriptional complexes that govern key physiological and pathological cell states. Hence, this work will contribute to a deeper understanding of gene regulation and the molecular basis of cell identity.