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The Polycomb repressor complex 2 (PRC2) is composed of the core subunits Ezh1/2, Suz12, and Eed, and it mediates all di- and tri-methylation of histone H3 at lysine 27 in higher eukaryotes. However, little is known about how the catalytic activity of PRC2 is regulated to demarcate H3K27me2 and H3K27me3 domains across the genome. To address this, we mapped the endogenous interactomes of Ezh2 and Suz12 in embryonic stem cells (ESCs), and we combined this with a functional screen for H3K27 methylation marks. We found that Nsd1-mediated H3K36me2 co-locates with H3K27me2, and its loss leads to genome-wide expansion of H3K27me3. These increases in H3K27me3 occurred at PRC2/PRC1 target genes and as de novo accumulation within what were previously broad H3K27me2 domains. Our data support a model in which Nsd1 is a key modulator of PRC2 function required for regulating the demarcation of genome-wide H3K27me2 and H3K27me3 domains in ESCs.
Pubmed ID: 29606589 RIS Download
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Web tool written in R for generation of box plots with R packages shiny, beanplot4, vioplot, beeswarm and RColorBrewer, and hosted on shiny server to allow for interactive data analysis. Data are held temporarily and discarded as soon as session terminates.Represents both summary statistics and distribution of primary data. Enables visualization of minimum, lower quartile, median, upper quartile and maximum of any data set.Data matrix can be uploaded as file or pasted into application. May be downloaded to run locally or as virtual machine for VMware and VirtualBox.
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