Mechanisms of inheritance of histone-based information through DNA replication.

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Epigenetic inheritance is the study of inherited information, which affects how cells use their genetic material (or express genes), rather than the genes themselves. Our genetic material, DNA, is packaged with proteins into a structure called chromatin. Chromatin consists of repeating units of histones, proteins that organize the long threads of DNA into fibers. The structure of chromatin fibers is not identical at all genes; different structures are used to indicate which genes should be on or off genes will be active or silenced. These differences in chromatin at different genes are thought to be inherited when cells divide; this inheritance helps the two new cells remember which genes to express. However, the molecular process by which cell divide disrupts chromatin structure. Cells are likely to have strategies to preserve the information in chromatin structures cell division. Our goal is to discover these strategies. When cells copy their DNA, the histone proteins are dislodged. They are then put back once the DNA is copied. However, we do not know if they are put back at exactly the same place or somewhere nearby. This is important because histones are not the same at genes that are active versus silenced. Thus, each gene may need to keep its “own” histones to ensure that the correct expression state is copied. Our experiments are designed to test how well genes keep their own histones, and the strategies that are used to put histones back near where they started. When the genetic material is duplicated, some of the histones are transferred to one copy, and some to the other. The gaps left between the histones are filled by new histones. However, these new histones are generic and do not have information about gene expression patterns. Thus, there need to be mechanisms to make the new histones the same as the old ones at each gene. The two new copies of the genome, referred to as “sisters”, are held together by a special protein complex called cohesin. Our project aims to test if the two new copies of the genome exchange information to ensure that the new histones on both copies are converted to the old state. The processes we are studying are essential for cells to maintain their identity, and may be disrupted in diseases like cancer that involve aberrant cell replication.