@article{e65a9cfce881459fa8e79811a58fafba,
title = "YAP-mediated recruitment of YY1 and EZH2 represses transcription of key cell-cycle regulators",
abstract = "The Hippo pathway regulates cell proliferation and organ size through control of the transcriptional regulators YAP (yesassociated protein) and TAZ. Upon extracellular stimuli such as cell-cell contact, the pathway negatively regulates YAP through cytoplasmic sequestration. Under conditions of low cell density, YAP is nuclear and associates with enhancer regions and gene promoters. YAP is mainly described as a transcriptional activator of genes involved in cell proliferation and survival. Using a genomewide approach, we show here that, in addition to its known function as a transcriptional activator, YAP functions as a transcriptional repressor by interacting with the multifunctional transcription factor Yin Yang 1 (YY1) and Polycomb repressive complex member enhancer of zeste homologue 2 (EZH2). YAP colocalized with YY1 and EZH2 on the genome to transcriptionally repress a broad network of genes mediating a host of cellular functions, including repression of the cell-cycle kinase inhibitor p27, whose role is to functionally promote contact inhibition. This work unveils a broad and underappreciated aspect of YAP nuclear function as a transcriptional repressor and highlights how loss of contact inhibition in cancer is mediated in part through YAP repressive function.",
author = "Sany Hoxha and Alyssa Shepard and Scott Troutman and Huitian Diao and Doherty, {Joanne R.} and Michalina Janiszewska and Witwicki, {Robert M.} and Pipkin, {Matthew E.} and Ja, {William W.} and Kareta, {Michael S.} and Kissil, {Joseph L.}",
note = "Funding Information: We thank Dr. Ursula Ehmer (Roman-Herzog-Krebszentrum-Comprehensive Cancer Center) for sharing vectors used in the tail vein injections. Library preparation and sequencing were performed at The Scripps Research Institute Florida Genomics Core. The work was supported by grants R01NS077952 (NINDS/NIH) and R01CA124495 (NCI/NIH to J.L. Kissil) and R01AG045036 (to W.W. Ja from the NIA/NIH). M.S. Kareta was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the NIH under grant number P20GM103620. M.E. Pipkin was supported by R01AI095634 (NIAID/ NIH) and the Frenchman's Creek Women for Cancer Research. Funding Information: We thank Dr. Ursula Ehmer (Roman-Herzog-Krebszentrum- Comprehensive Cancer Center) for sharing vectors used in the tail vein injections. Library preparation and sequencing were performed at The Scripps Research Institute Florida Genomics Core. The work was supported by grants R01NS077952 (NINDS/NIH) and R01CA124495 (NCI/NIH to J.L. Kissil) and R01AG045036 (to W.W. Ja from the NIA/NIH). M.S. Kareta was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the NIH under grant number P20GM103620. M.E. Pipkin was supported by R01AI095634 (NIAID/ NIH) and the Frenchman's Creek Women for Cancer Research. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = jun,
doi = "10.1158/0008-5472.CAN-19-2415",
language = "English (US)",
volume = "80",
pages = "2512--2522",
journal = "Cancer Research",
issn = "0008-5472",
number = "12",
}