Understanding how Trithorax & Polycomb group proteins control gene expression from CpG islands

Summary of proposed research: Chromatin is a complex of DNA and histone proteins. Chromatin tightly packs DNA so that it can fit into the nuclei of cells and regulates gene expression. Most cells in complex, multicellular organisms contain the same DNA, regulation of gene expression determines their fate and function. Aberrant gene expression regulation is the cause of many diseases. Histones are modified, by addition of various chemical groups by a range of proteins. Different modifications have different effects on gene expression. Histone modifiers can be grouped as either Polycomb repressive or Trithorax activating group proteins, which regulate gene expression from GC-rich, unmethylated DNA known as CpG islands (CGIs). We aim to build upon unpublished data, by engineering cell lines via CRISPR, with degron tags attached to core Trithorax/Polycomb group proteins, to study their effects on gene expression, with next-generation sequencing techniques such as ChIP-seq and tt-seq. We also propose an interdisciplinary methodology, combining in silico structural analysis, fluorescence imaging and next-generation sequencing techniques, with the aim of discovering novel CGI-binding proteins and their potential roles in regulating gene expression. Our proposed research will further our understanding of fundamental Human biology, and aid development of therapeutics/diagnostics for diseases caused by aberrant gene expression.
BBSRC research priority areas: Understanding the rules of life; Bioscience for an integrated understanding of health