Research published last week in Nature documents the first production of a detailed working image of the group of enzymes termed Polycomb Repressive Complex 1 (PRC1), which could provide new insight into the development of cancer cells.
PRC1, which is related to the BRCA1 breast cancer protein, is an enzyme group that is responsible for the regulation of cell development and has frequently been linked to many different forms of cancer.
More specifically, PRC1 is able to turn genes on or off by manipulating individual nucleosomes. “The nucleosome is a key target of the enzymes that conduct genetic processes critical for life,” explained Song Tan, the lead author of the study (Penn State University, PA USA).
By obtaining this working image of PRC1, the team at Penn State University has documented the first crystal structure of a gene regulation enzyme at work on a nucleosome.
The image reveals the previously unknown process of attachment of the cancer-related enzyme to its nucleosome target. The information documented in the image includes the exact nature of the interaction between enzymes in the PRC1 group and the nucleosomes, and the crystal structure of a multisubunit protein complex bound to a nucleosome.
The production of this image is the culmination of over 12 years of research at the Tan laboratory, who have also determined the first structure of another nucleosome-bound protein, RCC1. “This [PRC1] is the second important structure from the Tan lab to date of a nucleosome in complex with a protein known to interact with and modify chromatin behavior, which in turn can influence human gene expression,” commented Peter Preusch of the National Institute of General Medical Sciences (MD, USA). “Along with Dr Tan’s previous work detailing a nucleosome bound to the key regulatory protein, RCC1, this new structure adds to our knowledge of how proteins can regulate the structure and function of our genetic material.”
The research carried out in the Penn State Center for Eukaryotic Gene Regulation may also provide insight into the workings of the related BRCA1 protein. “Our study suggests that BRCA1 and PRC1 employ a similar mechanism to anchor to the nucleosome,” Tan said.
Tan and his team are now working to visualize how BRCA1 and other disease-related chromatin enzymes interact with the nucleosome.