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H3K27me3-human antibody

RRID:AB_2616019

Antibody ID

AB_2616029

Target Antigen

H3K27me3 homo sapiens

Proper Citation

(Cell Signaling Technology Cat# 9733, RRID:AB_2616029)

Clonality

unknown

Comments

ENCODE PROJECT External validation DATA SET is released testing lot 10 for not specified; status is awaiting lab characterization. ENCODE PROJECT External validation DATA SET is released testing lot 1 for not specified; status is not eligible for new data. ENCODE PROJECT External validation DATA SET is released testing lot 1 for any cell type or tissues; status is awaiting lab characterization. Consolidated with AB_1147656, and AB_1147655 on 09/21/16

Host Organism

rabbit

Vendor

Cell Signaling Technology Go To Vendor

Cat Num

9733 also ENCAB155VEG

Publications that use this research resource

H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers.

  • Fang D
  • Elife
  • 2018 Jun 22

Literature context:


Abstract:

Expression of histone H3.3K27M mutant proteins in human diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here, we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes.

Funding information:
  • National Institutes of Health - CA204297()
  • NIGMS NIH HHS - GM107466(United States)

Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2.

  • Lee CH
  • Mol. Cell
  • 2018 May 3

Literature context:


Abstract:

The maintenance of gene expression patterns during metazoan development is achieved, in part, by the actions of polycomb repressive complex 2 (PRC2). PRC2 catalyzes mono-, di-, and trimethylation of histone H3 at lysine 27 (H3K27), with H3K27me2/3 being strongly associated with silenced genes. We demonstrate that EZH1 and EZH2, the two mutually exclusive catalytic subunits of PRC2, are differentially activated by various mechanisms. Whereas both PRC2-EZH1 and PRC2-EZH2 are able to catalyze mono- and dimethylation, only PRC2-EZH2 is strongly activated by allosteric modulators and specific chromatin substrates to catalyze trimethylation of H3K27 in mouse embryonic stem cells (mESCs). However, we also show that a PRC2-associated protein, AEBP2, can stimulate the activity of both complexes through a mechanism independent of and additive to allosteric activation. These results have strong implications regarding the cellular requirements for and the accompanying adjustments in PRC2 activity, given the differential expression of EZH1 and EZH2 upon cellular differentiation.

Funding information:
  • NIAID NIH HHS - AI071121(United States)

Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin.

  • Lee CH
  • Mol. Cell
  • 2018 May 3

Literature context:


Abstract:

PRC2 is a therapeutic target for several types of cancers currently undergoing clinical trials. Its activity is regulated by a positive feedback loop whereby its terminal enzymatic product, H3K27me3, is specifically recognized and bound by an aromatic cage present in its EED subunit. The ensuing allosteric activation of the complex stimulates H3K27me3 deposition on chromatin. Here we report a stepwise feedback mechanism entailing key residues within distinctive interfacing motifs of EZH2 or EED that are found to be mutated in cancers and/or Weaver syndrome. PRC2 harboring these EZH2 or EED mutants manifested little activity in vivo but, unexpectedly, exhibited similar chromatin association as wild-type PRC2, indicating an uncoupling of PRC2 activity and recruitment. With genetic and chemical tools, we demonstrated that targeting allosteric activation overrode the gain-of-function effect of EZH2Y646X oncogenic mutations. These results revealed critical implications for the regulation and biology of PRC2 and a vulnerability in tackling PRC2-addicted cancers.

Funding information:
  • NIDDK NIH HHS - R01-DK-51729(United States)