Polycomb Complex 2 Is Required for <i>E-cadherin</i> Repression by the Snail1 Transcription Factor

Herranz, Nicolás; Pasini, Diego; Dı́az, Vı́ctor M.; Francı́, Clara; Gutiérrez, Arantxa; Dave, Natàlia; Escrivà, Maria; Hernandez-Muñoz, Inma; Croce, Luciano Di; Helin, Kristian; Herreros, Antonio Garcı́a de; Peiró, Sandra

doi:10.1128/mcb.00323-08

Cited by 397 publications

(340 citation statements)

References 42 publications

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“…Therefore, it is not difficult to understand why siSnail, but not siYY1 dissociated EZH2 and HDAC1/2 from the YY1 region of Ecadherin promoter. As a result of our collective present data, together with other group's findings (van der Vlag and Otte, 1999;Peinado et al, 2004;Herranz et al, 2008;von Burstin et al, 2009), herein we propose a main co-repressor complex, that is, EZH2/HDAC1/2/Snail, in the regulation of E-cadherin in NPC cells, and probably in a number of other types of human cancers. A schematic representation of the major molecular mechanisms of this complex, in NPC cells, is suggested and provided in Figure 5d.…”

Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Alsupporting

confidence: 84%

“…Recently, Herranz et al (2008) found that zinc-finger factor Snail could recruit PRC2 complex to the E-cadherin promoter (Herranz et al, 2008). In this study, we found that the repressive activity of EZH2 in E-cadherin expression was virtually completely prevented, when Snail was knocked down in NPC cells.…”

Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Almentioning

confidence: 54%

“…Such caused the stabilization of Snail via activation of PI3K/AKT signaling and ultimately inhibited E-cadherin expression; EZH2 was also detected at the PTEN promoter locus (Song et al, 2009). In addition, the repressive function of PRC2 is required for PRC1 recruitment to target genes (Cao et al, 2002;Boyer et al, 2006;Simon and Lange, 2008), and PRC2 inactivation by Suz12 siRNA was found to increase mRNA levels of PTEN (Herranz et al, 2008;Song et al, 2009). These results suggest that EZH2 might also downregulate PTEN and consequently involve the PI3K/AKT/Snail pathway to repress E-cadherin.…”

Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Almentioning

confidence: 99%

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EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin

et al. 2011

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The enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype (Po0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo, whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs.

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Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Alsupporting

confidence: 84%

Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Almentioning

confidence: 54%

Section: Ezh2 Promotes Npc Cell Aggressiveness Z-t Tong Et Almentioning

confidence: 99%

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EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin

et al. 2011

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“…Accumulating evidences suggest that some regulatory elements, such as transcription factors and non-coding RNAs, may recruit certain enzymes to specific DNA regions (34). For example, the transcription factor SNAIL1 recruits to the Ecadherin promoter region histone demethylase LSD1 that removes H3K4me2 (35), histone deacetylase 1 (HDAC1) and HDAC2 (36), and PRC2, an H3K27me3 methyltransferase (37). In addition, some enzymes, e.g.…”

Section: Insert Figurementioning

confidence: 99%

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

Xing

Jin

Zhang

et al. 2015

Epigenetic Technological Applications

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(100-250 words)How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes differentiate reproducibly from a single fertilized egg? These are fundamental problems in developmental biology. Epigenetic histone modifications play an important role in the maintenance of different cell phenotypes. The exact molecular mechanism for inheritance of the modification patterns over cell generations remains elusive. The complexity comes partly from the number of molecular species and the broad time scales involved. In recent years mathematical modeling has made significant contributions on elucidating the molecular mechanisms of DNA methylation and histone Book chapter in Epigenetic Technological Applications (Elsevier), in press 2 covalent modification inheritance. We will pedagogically introduce the typical procedure and some technical details of performing a mathematical modeling study, and discuss future developments. Keywords (5-10)Histone epigenetic memory, mathematical modeling, reader and writer, pattern reconstruction, stochastic dynamics, histone modification enzyme, post-translational modification Outline:In this chapter we discuss how to use mathematical modeling to explore the dynamics and mechanism of histone modification dynamics. Book chapter inEpigenetic Technological Applications (Elsevier), in press 3 Textbody

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“…Repression of E-cadherin is a molecular marker of EMT. Studies have demonstrated that EZH2 and Suz12 mediate transcriptional silencing of the tumor suppressor gene E-cadherin by trimethylation of histone H3 lysine 27 [14,15], which promotes the metastasis of cancer. These observations provide a functional link between the dysregulation of PRC2 and the repression of E-cadherin during cancer progression.…”

Section: Epithelial Mesenchymal Transitionmentioning

confidence: 99%

Polycomb group proteins and their roles in carcinogenesis

Xiao

Tao

et al. 2012

Chin. Sci. Bull.

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In the cell nucleus, DNA is wound around histone proteins, which are then packed together to form chromatin. Histones can be chemically tagged by methyl and acetyl groups. Polycomb group (PcG) proteins attach methyl groups to genes, which block their activity. This is similar to the attachment of methyl groups to gene promoters by DNA methyltransferases (DNMTs). This action is directly linked with tumor initiation and metastasis via the promotion of anti-senescence and anti-apoptosis pathways, and by facilitating epithelial mesenchymal transition (EMT). Cell fate transcriptional factors (CFTFs) and long non-coding RNAs (long ncRNAs) recruit PcG proteins to the promoters of tumor suppressor genes, resulting in epigenetic gene silencing by influencing chromatin structure and DNA accessibility. Thus, PcG proteins are potential diagnostic markers and targets for new chemoprevention and therapeutic strategies. Tumorigenesis has traditionally been considered to be driven by the sequential acquisition of mutations, leading to the activation of oncogenes and to the loss of function of tumor suppressor genes. An increasingly large amount of evidence suggests that carcinogenesis also involves "epigenetic changes", which are mediated by mechanisms that do not affect the primary DNA sequence. Epigenetic changes include both genome-wide loss and regional gain of DNA methylation, and aberrant post-translation modifications of histones. Both DNA methylation and histone modification have key functions in governing gene expression by influencing chromatin structure and DNA accessibility. Abnormal chromatin structure can cause inappropriate gene expression and genomic instability, which results in cellular transformation and malignant growth. Therefore, proteins that control chromatin structure are important in carcinogenesis. Polycomb group proteins (PcG proteins), which regulate chromatin remodeling, are one such class of proteins that regulate chromatin structure. PcG proteins form multiprotein repressive complexes, called polycomb repressive complexes (PRCs). As repressors of transcription, PRCs silence specific genes by altering chromatin modification. Here we review the biological functions and the molecular mechanisms of PcG proteins in oncogenesis. We also consider the potential role of PcG proteins in the diagnosis and treatment of cancer.

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Polycomb Complex 2 Is Required for E-cadherin Repression by the Snail1 Transcription Factor

Cited by 397 publications

References 42 publications

EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin

EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

Polycomb group proteins and their roles in carcinogenesis

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