Job Title: UAF in Pervasive Transcription
The main objective of my research is to understand the roles of epigenetic control in gene expression. A major form of epigenetic information is the covalent modification of histone proteins that form part of chromatin. The patterns of the histone modifications are associated with gene activity, and some modifications themselves have been shown to control genomic activity. Trimethylation of histone H3 lysine 4 (H3K4me3) is considered to be the “promoter mark” and is mainly implemented by the COMPASS complex across eukaryotes. This complex contains CXXC1/CFP-1, an unmethylated CpG binding protein that targets CpG island promoters, and is required for H3K4me3 modification at mammalian promoter regions. Misregulation of H3K4 methylation is likely to lead to human diseases, however neither the function nor the mechanism of action of H3K4me3 is well understood.
During my Post-Doctoral research in Cambridge, I discovered C. elegans and human promoter-enhancer architectures share strong similarities. For instance, in both organisms, transcription is frequently initiated bi-directionally at promoters and enhancers, showing that pervasive transcription is wide spread. I also demonstrated that the C. elegans CFP-1 protein targets CpG-dense promoters that are marked by H3K4me3, which was unexpected as DNA methylation is absent in C. elegans. In addition, C. elegans genetics combined with genome-wide RNAi screens provide a powerful system to identify novel genes that function together in a process. I have already completed a primary screen and found nuclear factors that suppress the sterility of C. elegans cfp-1 mutants.
As a University Academic Fellow here in Leeds, I will continue my investigation in the function of CFP-1 and its genetic interactors in chromatin structure and gene expression. I will use genetic approaches (e.g. CRISPR-Cas9 genome editing) and molecular/ biochemical tools in C. elegans and human cells to study the conserved regulatory roles of epigenetic control in chromatin function and gene regulation.