Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "EED"

EED

Official Full Name
embryonic ectoderm development
Organism
Homo sapiens
GeneID
8726
Background
This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Synonyms
HEED; COGIS; WAIT1;
Protein Sequence
MSEREVSTAPAGTDMPAAKKQKLSSDENSNPDLSGDENDDAVSIESGTNTERPDTPTNTPNAPGRKSWGKGKWKSKKCKYSFKCVNSLKEDHNQPLFGVQFNWHSKEGDPLVFATVGSNRVTLYECHSQGEIRLLQSYVDADADENFYTCAWTYDSNTSHPLLAVAGSRGIIRIINPITMQCIKHYVGHGNAINELKFHPRDPNLLLSVSKDHALRLWNIQTDTLVAIFGGVEGHRDEVLSADYDLLGEKIMSCGMDHSLKLWRINSKRMMNAIKESYDYNPNKTNRPFISQKIHFPDFSTRDIHRNYVDCVRWLGDLILSKSCENAIVCWKPGKMEDDIDKIKPSESNVTILGRFDYSQCDIWYMRFSMDFWQKMLALGNQVGKLYVWDLEVEDPHKAKCTTLTHHKCGAAIRQTSFSRDSSILIAVCDDASIWRWDRLR
Open
Disease
Diffuse large B-cell lymphoma, Prostate cancer
Approved Drug
0
Clinical Trial Drug
2 +
Discontinued Drug
0

Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price

Detailed Information

A key member of the Polycomb group (PcG) protein family is EED (Embryonic Ectoderm Development). Originally found in Drosophila as repressors of Hox genes, PcG proteins are now extensively important in multicellular development via controlling transcriptional silence of genes in mammals. At the core of the Polycomb Repressive Complex 2 (PRC2), the EED protein mostly controls gene silence by histone methylation, therefore influencing processes including cell proliferation, differentiation, and embryonic development.

Core subunits making up the PRC2 complex are EZH2, SUZ12, EED, and RBAP4/7. EED interacts with EZH2 through its WD40 repeat domain as a major component of the PRC2 complex, therefore helping the assembly and activation of the complex. On histone H3 (H3K27me3), PRC2 catalyzes the trimethylation of lysine 27, therefore suppressing the expression of particular genes. Stabilizing EZH2 activity throughout this process depends critically on EED, therefore guaranteeing the correct operation of PRC2.

Interaction Between EED and EZH2

EZH2 is a pivotal component of PRC2, showing histone methyltransferase activity through its SET domain, enabling methylation of lysine residues on histone H3. However, without the support of other subunits, EZH2 is usually auto-inhibited and largely inactive. During PRC2 assembly, EED is crucial for EZH2 activation by binding to its N-terminal region via the WD40 repeat domain, thus promoting robust methyltransferase activity and catalyzing H3K27 trimethylation. This epigenetic repressive mark not only inhibits target gene transcription but also aids in PRC2 chromatin binding.

EED's Relationship with Histone Methylation

Beyond its role in PRC2 assembly, EED recognizes H3K27me3 modifications through its aromatic cage structure. By binding to H3K27me3, EED enhances PRC2 enzymatic activity and establishes extensive methylation domains on chromatin. This mechanism is crucial for transcriptional repression and gene silencing propagation. EED's aromatic cage specifically recognizes and binds to H3K27me3, increasing PRC2 affinity for chromatin and facilitating genomic positioning.

Role of EED in Embryonic Development

In multicellular organisms, precise gene expression regulation is essential for determining cell fate during embryonic development. As a vital component of PRC2, EED contributes to pluripotency maintenance in embryonic stem cells and determines cell lineage during embryogenesis. EED regulates PRC2 activity to ensure specific gene silencing, promoting differentiation of particular cell types. Additionally, EED supports self-renewal and pluripotency of embryonic stem cells, making it a crucial target in developmental biology research.

Figure 1 illustrates the role of EED protein in various organ morphogenesis processes, such as embryonic development, spermatogenesis, oogenesis, and neurogenesis, with its absence in the Polycomb Repressive Complex 2 leading to multiple developmental abnormalities.Figure 1. EED protein is crucial for normal morphogenesis in several developmental processes, with its absence causing significant developmental defects. (Huang L, et al., 2023)

EED's Relationship with Cancer

Recently, EED has emerged as an important epigenetic target in cancer research. Studies indicate that EED and the PRC2 complex play significant roles in cancer development and progression. EED maintains cancer cell proliferation and suppresses tumor suppressor gene expression through gene silencing regulation, promoting cancer growth. Consequently, developing EED inhibitors represents a promising direction in cancer therapy.

Some EED inhibitors have entered clinical trials, demonstrating positive therapeutic effects. For instance, EPZ-6438 (tazemetostat) targets EED, showing potential in treating certain cancer types by reshaping chromatin and restoring normal gene expression patterns, thus inhibiting cancer cell growth. This direction not only highlights EED's potential in cancer treatment but also offers new avenues for diseases linked to abnormal gene expression.

EED in Epigenetic Function

As an important epigenetic regulator, EED is involved in PRC2 assembly and activation, playing a critical role in gene silencing. Through interactions with EZH2 and H3K27me3, EED influences chromatin state and gene expression. EED can recognize H3K27me3 marks and interact with other epigenetic marks like H3K9me3 and H4K20me3, collectively promoting gene silencing and epigenetic repression.

EED's functionalities make it a significant target for studying epigenetics and gene regulation. As understanding of EED's functions deepens, research is exploring strategies to modulate EED activity to address aberrant gene expression and related diseases, opening new prospects for epigenetic therapeutic applications.

 EED's Structure and Mechanism

EED is part of the WD40 repeat protein family, characterized by seven WD40 repeat domains at its C-terminus, forming a seven-bladed β-propeller structure. This domain facilitates interactions with other proteins, notably binding EZH2, stabilizing its activity, and promoting PRC2 assembly and catalytic function.

Furthermore, EED's aromatic cage recognizes H3K27me3 trimethylation, regulating PRC2 chromatin spread, an essential mechanism for PRC2-mediated genomic silencing, and a core function of EED in gene expression regulation.

 EED's Mechanism in Gene Silencing

Through H3K27me3 interaction, EED promotes PRC2 assembly and activation, stabilizing EZH2 and promoting H3K27 methylation, creating broad silencing marks on chromatin. The PRC2 complex uses this mechanism to suppress specific genes in the genome, maintaining normal cell development and function.

EED's aromatic cage interacts with other epigenetic marks, enhancing PRC2 affinity for chromatin, and further promoting gene silencing. This mechanism provides new insights into gene regulation and lays a foundation for epigenetic therapy applications.

EED's Role in Development and Disease

EED's developmental role extends beyond gene silencing, participating in cell fate and lineage choices. It regulates PRC2 activity during development, ensuring precise spatiotemporal gene expression, and facilitating different cell type formation. Its developmental importance makes EED a focal point in developmental biology research.

In disease, aberrant EED expression is linked to various disorders, especially cancer and genetic diseases. EED regulates gene expression in PRC2, involved in cell proliferation and differentiation, where dysfunction may lead to gene expression imbalance and disease manifestation. Developing EED inhibitors offers new treatment possibilities for cancer and genetic expression disorders.

References:

  1. Zhai J, Xiao Z, et al. Human embryonic development: from peri-implantation to gastrulation. Trends Cell Biol. 2022 Jan;32(1):18-29.
  2. Huang L, Li F, et al. Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis. Cell Prolif. 2023 Apr;56(4):e13413.
  3. Zhao Y, Guan YY, et al. Recent strategies targeting Embryonic Ectoderm Development (EED) for cancer therapy: Allosteric inhibitors, PPI inhibitors, and PROTACs. Eur J Med Chem. 2022 Mar 5;231:114144.
Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

Fax

Email

USA

Germany

Copyright © Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy