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Epigenetic refers to heritable changes in gene expressions that do not involve alteration of DNA sequence. Epigenetic mechanisms such as histone post-translational modification, ATP-dependent chromatin remodeling, and histone variance play central role in determining when and where genes are turned on and off in normal development and in diseases. The precision of these events relies on the proper functions of key players in these epigenetic processes. These epigenetic factors usually exist as multi-subunit protein complexes that directly or indirectly modulate the chromatin structure to achieve downstream affects. It is not surprising that their deregulation or mutations are linked to many forms of cancers. Of particular interest to us are the ATP-dependent chromatin remodelers and the Polycomb (PcG) Repressive Complexes. In general, PcG proteins inhibit transcription by maintaining a repressive chromatin structure, while ATP-dependent chromatin remodelers enhance transcription by generating a permissive chromatin structure. We are interested in understanding the structure-function relationship of these complexes. By using a combination of single-particle cryo-electron microscopy (cryo-EM) and various biochemical and biophysical methods, we aim to gain molecular insights into the mechanism of how these sophisticated machineries function in normal development and in disease.