Roles of enhancer of zeste homolog 2: From skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis

Marchesi, Irene; Giordano, Antonio; Bagella, Luigi

doi:10.4161/cc.27921

Cited by 30 publications

(28 citation statements)

References 166 publications

(209 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding that EZH2 attenuates osteoblastogenesis is relevant to skeletal deformities seen in congenital human disorders and consistent with accruing data on epigenetic regulation of osteoblast differentiation (22,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)59). Our initial studies with mice lacking functional Ezh2 expression in mesenchymal progenitor cells show premature closure of the cranial sutures characteristic of craniosynostosis.…”

Section: Discussionsupporting

confidence: 89%

“…Polycomb group proteins, which assemble into polycombrepressive complex 1 and 2 (PRC1 and PRC2), are conserved genes that suppress gene expression to ensure proper embryonic development, stem cell maintenance, and differentiation (22). PRC1 hinders the ATP activity of SWI-SNF complex at the nucleosome and induces chromatin compaction (23).…”

mentioning

confidence: 99%

“…PRC1 hinders the ATP activity of SWI-SNF complex at the nucleosome and induces chromatin compaction (23). The PRC2 complex possesses histone methyltransferase activity and is responsible for the methylation of histone 3 at lysine 27 (H3K27) (22). EZH2, the enzymatic subunit of PRC2, catalyzes mono-, di-, and trimethylation of H3K27; reduces chromatin accessibility; and promotes gene silencing (24 -27).…”

mentioning

confidence: 99%

“…EZH2, the enzymatic subunit of PRC2, catalyzes mono-, di-, and trimethylation of H3K27; reduces chromatin accessibility; and promotes gene silencing (24 -27). An alternative PRC2 complex that contains EZH1 (enhancer of zeste homolog1)exists.ThePRC1-EZH1complexhaslowhistonemeth-ylation activity and is believed to compact the chromatin through a different mechanism (22). Thus, PRC1 and PRC2 complexes are critical in the establishment of compacted chromatin and together suppress gene expression.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2

Dudakovic

Camilleri

et al. 2015

Journal of Biological Chemistry

150

180

View full text Add to dashboard Cite

Background: Osteogenic differentiation is initiated by transcriptional and post-transcriptional epigenetic mechanisms. Results: Inhibition of H3K27 methyltransferase EZH2 enhances osteogenic commitment of human mesenchymal progenitors, and its depletion in mouse mesenchymal cells causes multiple skeletal abnormalities. Conclusion: EZH2 is required for skeletal patterning and bone formation. Significance: EZH2-dependent epigenetic mechanisms control osteogenesis both in vitro and in vivo.

show abstract

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2

Dudakovic

Camilleri

et al. 2015

Journal of Biological Chemistry

150

180

View full text Add to dashboard Cite

show abstract

“…SUZ12 and EED stimulates H3K27 histone methyltransferas increasing more than 1000 fold the catalytic activity of EZH2 alone whereas RbAp46 is responsible for the histone binding [13] . EZH1 is a homologue of EZH2, which originates an alternative PRC2 complex, however, data about this protein are sometimes contrasting [27] . It has been demonstrated that EZH1, in embryonic stem (ES) cells, is able to trimethylates H3K27, contributing to the silencing of a subset of developmental genes.…”

Section: Polycomb Group Proteinsmentioning

confidence: 99%

Targeting Enhancer of Zeste Homolog 2 as a promising strategy for cancer treatment

Marchesi

Bagella

2016

WJCO

Self Cite

View full text Add to dashboard Cite

Polycomb group proteins represent a global silencing system involved in development regulation. In specific, they regulate the transition from proliferation to differentiation, contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs. Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2, which induces transcriptional inhibition through the tri-methylation of histone H3, an epigenetic change associated with gene silencing. EZH2 expression is high in precursor cells while its level decreases in differentiated cells. EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis. Indeed, aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes, resulting in an uncontrolled proliferation and tumor formation. This editorial explores the role of Polycomb repressive complex 2 in cancer, focusing in particular on EZH2. The canonical function of EZH2 in gene silencing, the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation, were summarized. Moreover, mutations of EZH2, responsible for an increased methyltransferase activity in cancer, were recapitulated. Finally, various drugs able to inhibit EZH2 with different mechanism were described, specifically underscoring the effects in several cancers, in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.

show abstract

12‐O‐tetradecanoylphorbol‐13‐acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells

Marchesi

Sanna

Fais

et al. 2017

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma that arises from muscle precursors affecting predominately children and young adults. It can be divided into two main classes: embryonal (eRMS) and alveolar rhabodomyosarcomas (aRMS). Despite the expression of early muscle specific genes, RMS cells fail to complete myogenesis even in differentiation conditions. We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a molecule able to induce differentiation in eRMS with a mechanism that involves the protein kinase C (PKC). In this paper we report that treatment with TPA reduces the expression of EZH2 without affecting levels of H3K27me3. The combination of TPA with GSK126, an inhibitor of the catalytic activity of EZH2, has a synergic effect on the induction of muscle differentiation in RD rhabdomyosarcoma cells, suggesting a new therapeutic combinatory approach for RMS treatment.

show abstract

Roles of enhancer of zeste homolog 2: From skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis

Cited by 30 publications

References 166 publications

Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2

Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2

Targeting Enhancer of Zeste Homolog 2 as a promising strategy for cancer treatment

12‐O‐tetradecanoylphorbol‐13‐acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells

Contact Info

Product

Resources

About