Grant: Operating Grant

We wish to understand how genes are told that they are to be silent, or that they should be expressed or 'on'. Most cells in an individual have the same DNA, and therefore the same genes. Specific tissues express only a subset of their genes, so understanding gene regulation is very important to understanding disease as well as normal human biology. A dramatic regulation of genes occurs on the X chromosome. The X chromosome is one of the pair of sex chromosomes, and females have two X chromosomes while males have one X and the Y chromosome. In order to keep the number of genes that are active the same between male and females one of the X chromosomes is silenced in females. This silencing spreads along the chromosome and our research is to find the regions of DNA that help or prevent this spread of silencing. We will do this by comparing the DNA around genes that get silenced with other regions that never get silenced. The DNA that is commonly found in silent or active regions will be tested for its ability to make other genes active or silent in female mouse cells. Identifying such regions of DNA will further our understanding of gene regulation, and will identify regions of DNA that can protect inserted DNA from silencing which could be useful for future gene therapy attempts.