Topic: Polycomb repressive complex 1

During mammalian neurodevelopment, the establishment of spatial and temporally appropriate gene expression programmes ensures the correct production of distinct neural and glial cell types. This process is partially regulated by the modification of chromatin structure by epigenetic complexes, including the Polycomb group (PcG) family of co-repressors. Genetic screening has identified several PcG mutations that are causally associated with a range of congenital brain disorders, yet the specific regulatory roles of Polycomb complexes during normal neurodevelopment is still unclear. Here, we inve

With age, differentiated cells undergo a progressive erosion of epigenetic landscape and loss of cellular identity. Specifically, epigenetic aging involves H3K27ac depletion at cellular identity genes and their subsequent repression, together with H3K27me3-mediated derepression of developmental genes, normally silenced in differentiated cells. Yet, it is unclear whether such a mechanism occurs in brain cells, particularly in neurons, and whether it might contribute to neurodegenerative process, such that at play in Huntington’s disease (HD), a striatal neurodegenerative disease. In previous st

Epigenetic mechanisms are leveraged throughout development to maintain gene activity states. The polycomb group family of proteins are an essential class of epigenetic regulator, critical for neurodevelopment. Polycomb Repressive Complex 1 alters chromatin through the deposition of H2A ubiquitination(H2AK119ub1), in contrast, Polycomb repressive deubiquitinase (PR-DUB) complex removes H2AK119ub1. The antagonistic relationship maintains the appropriate balance of H2AK119ub within the cell to control gene expression. MBD5 plays an important role in stabilizing the PR-DUB. Mutations in MBD5 gene