Transcriptional inhibitory chromatin state is an important epigenetic regulatory mechanism that finely regulates the correct spatiotemporal expression of developmental genes and determines the fate of cells. Its imbalance leads to various diseases such as tumors PcG proteins often form complexes to regulate histone modifications, with PRC1 catalyzing H2AK119 monoubiquitination (H2AK119ub1), PRC2 catalyzing H3K27 methylation (H3K27me), and PR-DUB removing H2AK119ub1 At present, the mechanism of action and structural basis of PRC1 and PRC2 are relatively clear, but little is known about PR-DUB H2AK119ub1 modification is the earliest discovered type of histone modification, which is indispensable for recruiting PRC2, depositing H3K27me3, enhancing PRC stability, and inhibiting the formation of advanced chromatin structures PR-DUB restricts the distribution and level of H2AK119ub1 in the genome by antagonizing PRC1 enzyme activity, thereby preventing the silencing of active genes and ensuring that PRC1 can stably exert inhibitory effects within the multi combed chromatin domain The mammalian PR-DUB complex binds to ASXL1/2 or 3 through a multi protein core composed of BAP1 and helper proteins such as HCFC1 and FOXK1/2 BAP1 is a ubiquitin hydrolase, but its activity depends on binding to the DEUBAD domain of ASXL protein When using free histones and peptides as substrates, PR-DUB can be de ubiquitinated indiscriminately, but its catalytic activity against nucleosome substrates is H2AK119 specific Previously, through the crystal structure analysis of Drosophila PR-DUB, the M ü ller team discovered a mechanism by which ASX increases the ubiquitin affinity of the BAP1 Drosophila homolog Calypso to mediate activation. Calypso ULD-Asx DEU interacts to form a complete ubiquitin binding pocket, but there is still a lack of structural analysis of PR-DUB binding to nucleosome substrates, and the factors determining the specific removal of H2AK119ub dependent on nucleosomes are still unclear Recently, Xu Ruiming, Zhu Bing, Institute of Biophysics, Chinese Academy of Sciences
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