Every cell in the body has the same genetic information, yet cells can grow to be as different as heart and brain. To a large extent, the packaging of DNA designs the cells and presages their functions by controlling which genes are turned on or off during development. Understanding how those gene regulation instructions are passed to daughter cells is what drives Yi Zhang. He is a leader in the burgeoning field of epigenetics, where researchers are searching for the mechanisms that control gene expression that are independent of the DNA sequence itself.
Zhang has been probing the details of epigenetic modifications and their roles in fundamental biology and disease. His recent series of papers describes discovery of many of the enzymes known to modify the packaging of DNA by proteins known as histones. He works with model organisms ranging from yeast to human cells, using a combination of biochemistry, molecular biology, cell biology, and genetics.
Zhang and his colleagues have built the foundation for understanding the interactions between the different types of markers that change DNA packaging in ways that silence or activate genes, such as the addition of small acetyl, methyl, phosphate, and ubiquitin molecules. He demonstrated the importance of methylation and ubiquitination of histones in silencing of an important group of genes that specify the proper location of body parts in developing organisms. He and his colleagues also showed that the same modifications participate in inactivation of one copy of the X chromosome in females. In addition, they identified a protein involved in attaching a methyl marker to histone, which is important in causing and sustaining leukemia.
Zhang plans to search for small molecules that could interfere with the epigenetic changes responsible for leukemia. He also wants to explore the role of epigenetic modification in stem cell biology, including defining the marks that commit and maintain differentiated cells and those that may change a specialized cell into a stem cell or other type of cell.
RESEARCH ABSTRACT SUMMARY:
Yi Zhang is interested in how epigenetic modification-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment, stem cell pluripotency and self-renewal, and the development and treatment of human diseases.
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Photo: Karen Tam/AP, © HHMI