AI Article Synopsis
- YAP1 is a key player in the Hippo pathway and is linked to various cancers, often showing increased activity due to mutations or amplification.
- The study reveals that TEAD transcription factors help YAP1 bind to chromatin across the genome, highlighting their crucial role in YAP1's transcriptional functions.
- YAP1 regulates gene expression mainly through distal enhancers marked by H3K27 acetylation, which are essential for the activity of related genes, offering new insights into YAP1's role in both healthy and cancerous cells.
Article Abstract
YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546604 | PMC |
| http://dx.doi.org/10.1371/journal.pgen.1005465 | DOI Listing |
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Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of and -family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications.
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