| Literature DB >> 31564638 |
Ana P Gomes1, Didem Ilter2, Vivien Low2, Adam Rosenzweig2, Zih-Jie Shen3, Tanya Schild2, Martin A Rivas4, Ekrem E Er5, Dylan R McNally4, Anders P Mutvei2, Julie Han2, Yi-Hung Ou2, Paola Cavaliere6, Edouard Mullarky4, Michal Nagiec2, Sejeong Shin2, Sang-Oh Yoon2, Noah Dephoure6, Joan Massagué5, Ari M Melnick4, Lewis C Cantley4, Jessica K Tyler3, John Blenis7.
Abstract
Metastasis is the leading cause of cancer mortality. Chromatin remodeling provides the foundation for the cellular reprogramming necessary to drive metastasis. However, little is known about the nature of this remodeling and its regulation. Here, we show that metastasis-inducing pathways regulate histone chaperones to reduce canonical histone incorporation into chromatin, triggering deposition of H3.3 variant at the promoters of poor-prognosis genes and metastasis-inducing transcription factors. This specific incorporation of H3.3 into chromatin is both necessary and sufficient for the induction of aggressive traits that allow for metastasis formation. Together, our data clearly show incorporation of histone variant H3.3 into chromatin as a major regulator of cell fate during tumorigenesis, and histone chaperones as valuable therapeutic targets for invasive carcinomas.Entities:
Keywords: CAF-1 complex; HIRA; chromatin remodeling; epigenetics; histone H3.3; histone chaperones; metastasis; tumor progression
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Year: 2019 PMID： 31564638 PMCID： PMC6801101 DOI： 10.1016/j.ccell.2019.08.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743