PlumX Metrics
Embed PlumX Metrics

YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers

Molecular Cell, ISSN: 1097-2765, Vol: 60, Issue: 2, Page: 328-337
2015
  • 217
    Citations
  • 0
    Usage
  • 280
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

The Hippo/YAP signaling pathway is a crucial regulator of tissue growth, stem cell activity, and tumorigenesis. However, the mechanism by which YAP controls transcription remains to be fully elucidated. Here, we utilize global chromatin occupancy analyses to demonstrate that robust YAP binding is restricted to a relatively small number of distal regulatory elements in the genome. YAP occupancy defines a subset of enhancers and superenhancers with the highest transcriptional outputs. YAP modulates transcription from these elements predominantly by regulating promoter-proximal polymerase II (Pol II) pause release. Mechanistically, YAP interacts and recruits the Mediator complex to enhancers, allowing the recruitment of the CDK9 elongating kinase. Genetic and chemical perturbation experiments demonstrate the requirement for Mediator and CDK9 in YAP-driven phenotypes of overgrowth and tumorigenesis. Our results here uncover the molecular mechanisms employed by YAP to exert its growth and oncogenic functions, and suggest strategies for intervention.

Bibliographic Details

Galli, Giorgio G; Carrara, Matteo; Yuan, Wei-Chien; Valdes-Quezada, Christian; Gurung, Basanta; Pepe-Mooney, Brian; Zhang, Tinghu; Geeven, Geert; Gray, Nathanael S; de Laat, Wouter; Calogero, Raffaele A; Camargo, Fernando D

Elsevier BV

Biochemistry, Genetics and Molecular Biology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know