Our group studies the structure and biological properties of chromatin. Chromatin is the combination of DNA and the proteins that package it and regulate its function. Chromatin resides inside the nucleus of the cell. We study how different regions of chromatin can form protected neighborhoods called domains, and how adjacent neighborhoods with different properties can be prevented from influencing each other. For example, chromatin may contain genes that are ‘active’ next to a ‘silent’ region. Certain elements of the DNA sequence serve as boundaries between such regions, preventing the silent region from affecting the active one. We identified several proteins that bind to these elements, and showed that these proteins have properties that could explain how they form boundaries.
We also study long-range chromatin organization. One protein, CTCF, attaches to many sites throughout the organism’s DNA. Individual CTCF molecules also tend to stick to one another, forming large loops of chromatin within the nucleus.Genes and regulatory elements in different loops tend to be ‘insulated’ from one another, helping to control gene expression. In other cases the CTCF interactions can help bring together two genes that are far apart on the DNA. We focus on long-range interactions between the insulin gene and other genes in human pancreatic beta cells.We want to understand how these chromatin structures relate to insulin gene expression and secretion of the hormone. Our recent results show that contacts over great distances are important in these processes.