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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE124743 | GEO | 2019/04/08

REPOSITORIES: GEO

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PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism.

Project description:Posterior fossa type A (PFA) ependymomas exhibit very low H3K27 methylation and express high levels of EZHIP (Enhancer of Zeste Homologs Inhibitory Protein, also termed CXORF67). Here we find that a conserved sequence in EZHIP is necessary and sufficient to inhibit PRC2 catalytic activity in vitro and in vivo. EZHIP directly contacts the active site of the EZH2 subunit in a mechanism similar to the H3 K27M oncohistone. Furthermore, expression of H3 K27M or EZHIP in cells promotes similar chromatin profiles: loss of broad H3K27me3 domains, but retention of H3K27me3 at CpG islands. We find that H3K27me3-mediated allosteric activation of PRC2 substantially increases the inhibition potential of EZHIP and H3 K27M, providing a mechanism to explain the observed loss of H3K27me3 spreading in tumors. Our data indicate that PFA ependymoma and DIPG are driven in part by the action of peptidyl PRC2 inhibitors, the K27M oncohistone and the EZHIP 'oncohistone-mimic', that dysregulate gene silencing to promote tumorigenesis.

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PFA Ependymoma-associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (RNA-seq)

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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (ChIP-Seq Ring1b)

Project description:to understand the genome wide alterations in PRC2-mediated K27me3 and PRC1 distribution caused by oncohistone K27M mutation or novel PRC2 inhibitor – EZHIP

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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (ChIP-Seq H2K27me3)

Project description:to understand the genome wide alterations in PRC2-mediated K27me3 and PRC1 distribution caused by oncohistone K27M mutation or novel PRC2 inhibitor – EZHIP

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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (ChIP-Seq CBX2)

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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism

Project description:Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism

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Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (ChIP-Seq H2K27me3)

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Project description:Ependymoma associated protein EZHIP inhibits PRC2 through a H3 K27M like mechanism (ChIP-Seq Ring1b)