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- W4285388619 endingPage "1213" @default.
- W4285388619 startingPage "1202" @default.
- W4285388619 abstract "Epigenetic remodeling is essential for oncogene-induced cellular transformation and malignancy. In contrast to histone post-translational modifications, how DNA methylation is remodeled by oncogenic signaling remains poorly understood. The oncoprotein YAP, a coactivator of the TEAD transcription factors mediating Hippo signaling, is widely activated in human cancers. Here, we identify the 5-methylcytosine dioxygenase TET1 as a direct YAP target and a master regulator that coordinates the genome-wide epigenetic and transcriptional reprogramming of YAP target genes in the liver. YAP activation induces the expression of TET1, which physically interacts with TEAD to cause regional DNA demethylation, histone H3K27 acetylation and chromatin opening in YAP target genes to facilitate transcriptional activation. Loss of TET1 not only reverses YAP-induced epigenetic and transcriptional changes but also suppresses YAP-induced hepatomegaly and tumorigenesis. These findings exemplify how oncogenic signaling regulates the site specificity of DNA demethylation to promote tumorigenesis and implicate TET1 as a potential target for modulating YAP signaling in physiology and disease." @default.
- W4285388619 created "2022-07-14" @default.
- W4285388619 creator A5007759682 @default.
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- W4285388619 creator A5072538188 @default.
- W4285388619 creator A5083778545 @default.
- W4285388619 creator A5087238383 @default.
- W4285388619 date "2022-07-14" @default.
- W4285388619 modified "2023-10-11" @default.
- W4285388619 title "YAP induces an oncogenic transcriptional program through TET1-mediated epigenetic remodeling in liver growth and tumorigenesis" @default.
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