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Polycomb- and Methylation-Independent Roles of EZH2 as a Transcription Activator.

Cell reports | 2018

Enhancer of Zeste 2 (EZH2) is the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which catalyzes histone H3 lysine 27 trimethylation (H3K27me3) at target promoters for gene silencing. Here, we report that EZH2 activates androgen receptor (AR) gene transcription through direct occupancy at its promoter. Importantly, this activating role of EZH2 is independent of PRC2 and its methyltransferase activities. Genome-wide assays revealed extensive EZH2 occupancy at promoters marked by either H3K27ac or H3K27me3, leading to gene activation or repression, respectively. Last, we demonstrate enhanced efficacy of enzymatic EZH2 inhibitors when used in combination with AR antagonists in blocking the dual roles of EZH2 and suppressing prostate cancer progression in vitro and in vivo. Taken together, our study reports EZH2 as a transcriptional activator, a key target of which is AR, and suggests a drug-combinatory approach to treat advanced prostate cancer.

Pubmed ID: 30517868 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P50 CA180995
  • Agency: NCI NIH HHS, United States
    Id: R50 CA211271
  • Agency: NCI NIH HHS, United States
    Id: R01 CA172384
  • Agency: NCI NIH HHS, United States
    Id: R01 CA227918
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007169

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

View all literature mentions

ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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JASPAR (tool)

RRID:SCR_003030

Open source database of curated, non-redundant set of profiles derived from published collections of experimentally defined transcription factor binding sites for multicellular eukaryotes. Consists of open data access, non-redundancy and quality. JASPAR CORE is smaller set that is non-redundant and curated. Collection of transcription factor DNA-binding preferences, modeled as matrices. These can be converted into Position Weight Matrices (PWMs or PSSMs), used for scanning genomic sequences. Web interface for browsing, searching and subset selection, online sequence analysis utility and suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. New functions include clustering of matrix models by similarity, generation of random matrices by sampling from selected sets of existing models and a language-independent Web Service applications programming interface for matrix retrieval.

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Primer3 (tool)

RRID:SCR_003139

Tool used to design PCR primers from DNA sequence - often in high-throughput genomics applications. It does everything from mispriming libraries to sequence quality data to the generation of internal oligos.

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BioVision (tool)

RRID:SCR_005057

An Antibody supplier

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Systems Transcriptional Activity Reconstruction (tool)

RRID:SCR_005622

A next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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HOMER (tool)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

View all literature mentions

LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

View all literature mentions

GenomeStudio (tool)

RRID:SCR_010973

Visualize and analyze data generated by all of Illumina''s platforms.

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Cluster (tool)

RRID:SCR_013505

Software R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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Microsoft Excel (tool)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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BWA (tool)

RRID:SCR_010910

Software for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.

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ModFit LT (tool)

RRID:SCR_016106

Modeling software for flow cytometry histograms. Models for cell-tracking dye studies and synchronized cell lines are built right into the software.

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Deeptools (tool)

RRID:SCR_016366

Python based tools to process, visualize and analyse high-throughput sequencing data, such as ChIP-seq, RNA-seq or MNase-seq. Implemented within Galaxy framework. Used to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches.

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Java Treeview (tool)

RRID:SCR_016916

Software as a cross platform gene expression visualization tool. Extensible viewer for microarray data in the PCL or CDT format. Interactive display of clustered gene expression data. Java application for visualizing large data matrices. It can load a dataset, cluster it, browse it, customize its appearance and export it into a figure.

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LNCaP (tool)

RRID:CVCL_0395

Cell line LNCaP is a Cancer cell line with a species of origin Homo sapiens (Human)

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SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

View all literature mentions

Cyclin D1 antibody (antibody)

RRID:AB_447956

This polyclonal targets Cyclin D1

View all literature mentions

EZH2-human (antibody)

RRID:AB_10694683

This unknown targets EZH2

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

Anti-trimethyl Histone H3 (Lys27) (antibody)

RRID:AB_10563660

This polyclonal targets trimethyl Histone H3 (Lys27)

View all literature mentions

H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

View all literature mentions

Anti-Androgen Receptor, PG-21 (antibody)

RRID:AB_310214

This polyclonal targets Androgen Receptor PG-21

View all literature mentions

normal rabbit IgG (antibody)

RRID:AB_737197

This unknown targets normal rabbit IgG

View all literature mentions

H3K27me3-human (antibody)

RRID:AB_2616029

This unknown targets H3K27me3

View all literature mentions

HA-probe Antibody (Y-11) (antibody)

RRID:AB_631618

This polyclonal targets HA-probe

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

22Rv1 (cell line)

RRID:CVCL_1045

Cell line 22Rv1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

LNCaP clone FGC (cell line)

RRID:CVCL_1379

Cell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

normal rabbit IgG (antibody)

RRID:AB_737197

This unknown targets normal rabbit IgG

View all literature mentions

Anti-Androgen Receptor, PG-21 (antibody)

RRID:AB_310214

This polyclonal targets Androgen Receptor PG-21

View all literature mentions

H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

View all literature mentions

HA-probe Antibody (Y-11) (antibody)

RRID:AB_631618

This polyclonal targets HA-probe

View all literature mentions

SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

EZH2-human (antibody)

RRID:AB_10694683

This unknown targets EZH2

View all literature mentions

LNCaP clone FGC (cell line)

RRID:CVCL_1379

Cell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

View all literature mentions

Anti-trimethyl Histone H3 (Lys27) (antibody)

RRID:AB_10563660

This polyclonal targets trimethyl Histone H3 (Lys27)

View all literature mentions

Anti-Androgen Receptor, PG-21 (antibody)

RRID:AB_310214

This polyclonal targets Androgen Receptor PG-21

View all literature mentions

H3K27me3-human (antibody)

RRID:AB_2616029

This unknown targets H3K27me3

View all literature mentions

Cyclin D1 antibody (antibody)

RRID:AB_447956

This polyclonal targets Cyclin D1

View all literature mentions

EZH2-human (antibody)

RRID:AB_10694683

This unknown targets EZH2

View all literature mentions

LNCaP clone FGC (cell line)

RRID:CVCL_1379

Cell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HA-probe Antibody (Y-11) (antibody)

RRID:AB_631618

This polyclonal targets HA-probe

View all literature mentions

normal rabbit IgG (antibody)

RRID:AB_737197

This unknown targets normal rabbit IgG

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

View all literature mentions

Cyclin D1 antibody (antibody)

RRID:AB_447956

This polyclonal targets Cyclin D1

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

H3K27me3-human (antibody)

RRID:AB_2616029

This unknown targets H3K27me3

View all literature mentions

Anti-trimethyl Histone H3 (Lys27) (antibody)

RRID:AB_10563660

This polyclonal targets trimethyl Histone H3 (Lys27)

View all literature mentions

22Rv1 (cell line)

RRID:CVCL_1045

Cell line 22Rv1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

22Rv1 (cell line)

RRID:CVCL_1045

Cell line 22Rv1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions