This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The epigenetic memory for maintenance and regulation of an appropriate gene expression is essential not only for differentiation, but also in later stages of development. Polycomb Group (PcG) proteins are involved in the epigenetic memory to regulate cell differentiation and proliferation. The deregulation of PcG protein is involved in various human cancers.PcG proteins are known to keep master regulatory genes repressed. They are found in two Polycomb Repressive Complexes (PRC1 and PRC2). PRC1 is composed of Psc, Ph, Pc, dRing1, and several other non-PcG proteins. PRC2 is a histone methyltransferase complex containing Esc,E(z), Suz(12), and Nurf55. It is known that the PRC1 and PRC2 complexes function in concerted manner to repress genes. The PRC2 methylates Lysine27 of histone 3 (H3K27), which is a silencing code for recruiting a PRC1 complex causing a high order compacted chromatin structure. Although it is known that E(z) contains a methyltransferase catalytic SET domain, the presence of other components (Esc, Suz12, Nurf55) is absolutely required for its activity. However, there is little known about the functions of other components, nor the structure of these proteins. Three dimensional structures of PRC2 or individual subunits will likely provide fruitful information about the function of PRC2 and its components.
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