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Genome-wide Profiling of H3K27ac binding in human MCF-7 cell lines

ABSTRACT: The histone methyltransferase EZH2 has been shown to function as a multifaceted molecule which can switch from a transcriptional repressor to an activator inducing a subset of genes that promote oncogenesis, including breast cancer. TfR-1, a key mediator in iron absorption, is highly expressed in a variety of tumors and associated with tumor grade, tumor stage and prognosis of patients. However, the known regulation mechanism of TfR-1 mainly remains on post-transcriptional level. To figure out whether TfR-1 expression is under epigenetic control, we examined the influence of EZH2 depletion and inhibition on TfR-1 expression in different subtypes of breast cancer cells. We discovered that EZH2 context-dependently modulates TfR-1 level and manipulates cellular iron uptake. Moreover, we identified TfR-1 as an NF-κB target gene which is positively regulated by EZH2 via constructing a complex with p65-p50 and transcription factor AP-1 in ER- cells. Inversely, TfR-1 is repressed by EZH2 and ER through histone methylation on its promoter in ER+ cells. These ﬁndings demonstrated an additional role of EZH2 in promoting breast cancer progression through iron homeostasis regulation and underscore the need for developing context-speciﬁc strategy for therapeutic targeting of epigenetic inhibition in breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132974 | GEO | 2019/06/20

REPOSITORIES: GEO

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Context-Specific Regulation of NF-?B Target Gene Expression by EZH2 in Breast Cancers

Project description:Both EZH2 and NF-?B contribute to aggressive breast cancer, yet whether the two oncogenic factors have functional cross-talk in breast cancer is largely unknown. Here, we uncover an unexpected role of EZH2 in conferring the constitutive activation of NF-?B target gene expression in ER-negative basal-like breast cancer cells. This function of EZH2 is independent of its histone methyltransferase activity but requires the physical interaction with RelA/RelB to promote the expression of NF-?B targets. Intriguingly, EZH2 acts oppositely in repressing NF-?B targets in ER-positive luminal-like breast cancer cells by interacting with ER and directing repressive histone methylation. Thus, EZH2 function as a double-facet molecule in breast cancers, functioning either as a transcriptional activator or repressor of NF-?B targets, in a cell context-dependent manner. These findings reveals an additional mechanism by which EZH2 promotes breast cancer progression and also underscore the need for developing context-specific strategy for therapeutic targeting of EZH2 in breast cancers. 12 samples were analyzed including three replicates of siNC CTRL and siEZH2 CTRL.

2011-08-14 | E-GEOD-30670 | biostudies-arrayexpress

Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers

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Targeted H3R26 deimination specifically facilitates ER binding by modifying nucleosome structure

2014-08-04 | E-GEOD-58177 | biostudies-arrayexpress

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