EED

Case Study 1: Dilibaerguli Shaliman, 2022

Epigenetic modifications by polycomb repressive complex (PRC) molecules appear to play a role in the tumorigenesis and aggressiveness of neuroblastoma (NB). Embryonic ectoderm development (EED) is a member of the PRC2 complex that binds to the H3K27me3 mark deposited by EZH2 via propagation on adjacent nucleosomes. The researchers herein investigated the molecular roles of EED in MYCN-amplified NB cells using EED-knockdown (KD) shRNAs, EED-knockout sgRNAs, and the EED small molecule inhibitor EED226. The suppression of EED markedly inhibited NB cell proliferation and flat and soft agar colony formation. A transcriptome analysis using microarrays of EED-KD NB cells indicated the de-repression of cell cycle-regulated and differentiation-related genes. The results of a GSEA analysis suggested that inhibitory cell cycle-regulated gene sets were markedly up-regulated. Furthermore, an epigenetic treatment with the EED inhibitor EED226 and the HDAC inhibitors valproic acid/SAHA effectively suppressed NB cell proliferation and colony formation.

Fig1. Western blotting analysis of EZH2, SUZ12, EED, and H3K27me1–3.

Fig2. WST-8 cell proliferation assay of NGP and IMR32 cells. EED226 concentrations were 0, 1, 2, 5, and 10 μM.

Case Study 2: Qipeng Liu, 2019

Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In this study, the researchers report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, they demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities.

Fig3. Purified EZH2 and EED were respectively mixed with AR (full length) and pulled down with anti-AR antibody and protein A beads.

Fig4. EED was depleted by shRNA in C4–2 cells.

Fig1. αvβ3 signaling pathway in prostate cancer cells. (Qipeng Liu, 2019)

Fig2. EED is the missing link that couples TNF-R1 to nSMase2. (Stephan Philipp, 2010)

EED involved in several pathways and played different roles in them. We selected most pathways EED participated on our site, such as Cellular Senescence, Cellular responses to stress, Chromatin modifying enzymes, which may be useful for your reference. Also, other proteins which involved in the same pathway with EED were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

EED has several biochemical functions, for example, chromatin binding, histone methyltransferase activity, identical protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by EED itself. We selected most functions EED had, and list some proteins which have the same functions with EED. You can find most of the proteins on our site.

EED has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with EED here. Most of them are supplied by our site. Hope this information will be useful for your research of EED.

EZH2; DNMT3B; DNMT1; PINK1