The DNA that you see on your computer is not the same as the DNA that cells see. This is because DNA in vivo is not linear: it is looped, localized and condensed. This results in specific sequences being more readable or accessible in some cells than in others and some sequences close together. For example, DNA compaction hides specific sequences from the cell; DNA looping brings distant sequences close together and DNA localization compartmentalizes DNA sequences to localized pools of transcription factors. Collectively DNA compaction, looping, and compartmentalization constitute the architecture of the genome.
We are interested in how changes in the architecture of the genome relates to cell identity over the course of development and disease. We study the requirement of genes that shape genome architecture in stem cells and their daughters as well as in normal and tumor cells. This cartoon shows a class of genes that affect architecture called insultors.
Method to measure effects of architecture on gene expression
We developed methods to screen for the effects of genome architecture on gene expression. We developed a quantitative assay to measure how gene position effects gene expression. We we can employ in any cell type including normal and cancer cells. See our 2008 Nature Genetics paper which established the assay.
Changes in genome architecture can affect cell fate
In collaboration with Tony Ip and his colleagues, we found a factor that affects the identify of stem cells.
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