Elucidating Epigenetic Interactions using ITC

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Malvern Panalytical

Professor Andreas Ladurner, currently Professor and Chair of the Department of Physiological Chemistry at Ludwig-Maximilians-University (Germany), conducted pioneering epigenetics research as a postdoctoral fellow at University of California Berkley. Using MicroCal Isothermal Titration Calorimetry (ITC) his work confirmed the interaction of a human bromodomain module to acetylated histone protein (Jacobson, et al, Science 288, 1422-1425 (2000)). In this video Professor Ladurner discusses the value of ITC in epigenetics research. Epigenetics refers to chemical modifications of the DNA and its associated histone proteins that control gene activity independent of the genetic code. There are dozens of identified proteins from animals and plants which are involved in creating, recognizing, and removing these epigenetic modifications (also called “marks”) on the histones and DNA making up chromatin. Epigenetic modifications are believed to be inherited during cell division, which will help in cell development and create the hundreds of cell types of the human body carrying the same genes. Epigenetic control is implicated in many diseases, including cancers and diabetes. To understand the function, activity, and specificity of chromatin-binding proteins, each interaction needs to be defined by biophysical in vitro assays, and the dissociation constant (KD) is an important parameter. ITC provides a direct and quantitative KD measurement of binding interactions. ITC provides more information beyond the KD, such as binding thermodynamics and binding stoichiometry, giving further insight into the specificity and selectivity of the interaction, the mechanism of binding, and the structure of the active binding domain of the chromatin binding proteins.