2011
DOI: 10.1158/1541-7786.mcr-10-0511
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Abstract: Polycomb group (PcG) proteins such as Enhancer of zeste homolog 2 (EZH2) are epigenetic transcriptional repressors that function through recognition and modification of histone methylation and chromatin structure. Targets of PcG include cell cycle regulatory proteins which govern cell cycle progression and cellular senescence. Senescence is a characteristic of melanocytic nevi, benign melanocytic proliferations that can be precursors of malignant melanoma. In this study, we report that EZH2, which we find abse… Show more

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Cited by 166 publications
(146 citation statements)
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“…In contrast, knockdown of HIF2A failed to rescue the hypoxia-induced repression of SUZ12 and EED and even further up-regulated EZH2 mRNA, further validating the role of HIF1-α, rather than HIF2-α, in repressing PRC2. As a functional readout of repressive PRC2 activity, we showed that hypoxia induced the expression of two known PRC2-repressed target genes, CDKN1A (encoding p21) and CDKN1C (encoding p57) (31,39,40), recapitulating the effect of EZH2 knockdown (Fig. 2E).…”
Section: Resultsmentioning
confidence: 78%
“…In contrast, knockdown of HIF2A failed to rescue the hypoxia-induced repression of SUZ12 and EED and even further up-regulated EZH2 mRNA, further validating the role of HIF1-α, rather than HIF2-α, in repressing PRC2. As a functional readout of repressive PRC2 activity, we showed that hypoxia induced the expression of two known PRC2-repressed target genes, CDKN1A (encoding p21) and CDKN1C (encoding p57) (31,39,40), recapitulating the effect of EZH2 knockdown (Fig. 2E).…”
Section: Resultsmentioning
confidence: 78%
“…For melanoma, this is best achieved in transgenic mice, in which melanoma is initiated and spontaneously grows in an undisturbed environment without prior ex vivo manipulation of tumour cells 52 . Indeed, the function of EZH2 in selected melanoma cell lines has been controversial and linked to control of proliferation or in vitro migration [28][29][30] . Taking advantage of an inducible and cKO strategy that allows functional gene investigation at different stages of disease in an intact environment, we show that Ezh2 plays a dual role during melanomagenesis.…”
Section: Discussionmentioning
confidence: 99%
“…In human melanoma cells, loss of EZH2 partially interfered with proliferation or invasion capacity, dependent on the cell line and the experimental set up used [28][29][30] . However, a study investigating EZH2 function in a physiological context of melanoma progression, from tumour initiation to metastatic disease, is still missing.…”
mentioning
confidence: 99%
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“…Depletion of EZH2 in melanoma cells leads to the removal of histone deacetylases from, and normalizes the acetylation of, the CDKN1A locus, and restores apoptosis. 47 Increased expression of EZH2 is tightly associated with uncontrolled proliferation in melanoma. Key pathways, such as RAS/RAF/MEK, AKT, and E2F1, involved in melanoma biology, also regulate EZH2 activity.…”
Section: Chromatin Remodelingmentioning
confidence: 99%