About the Project
After DNA replication, histone modifications are diluted two-fold, which could result in loss of epigenetic information. After DNA replication, the two sister chromatids are held together through the action of the cohesin complex. One way to buffer the effect of diluting the histones is if histone-based information can be “shared” through the pairing of sister chromatids. To test this idea, we will analyze the rate and extent of restoration of histone modifications in cells with disrupted sister pairing. The recognition of histone modifications by the enzymes that create them is believed to be important for re-establishing histone modifications after DNA replication (sometimes referred to as a read-write mechanism). In principle, this mechanism could function both in cis and in trans (i.e. between sisters). We will use in vitro experiments ranging from simply tethering modified and unmodified templates to in vitro replication in the presence or absence of sister cohesion to test this model. Together, the in vitro and in vivo approaches will test the idea that sister chromatids exchange epigenetic information to maintain chromatin states.
This project involves genome engineering, and analysis of chromatin in vivo (e.g. ChIP) in cultured cells. It also depends heavily on in vitro reconstitution of biochemical reactions, including histone modification and DNA replication. This aspect of the project will require protein purification, chromatin assembly, and extract preparation (from Xenopus eggs).
Background in molecular biology and biochemistry or biophysics is highly recommended, but the most important characteristics are motivation, ability to work independently, and willingness to learn. We would also welcome students with more theoretical or computational backgrounds.
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