Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization

Publication date: Available online 26 September 2019Source: Cancer CellAuthor(s): Ana P. Gomes, Didem Ilter, Vivien Low, Adam Rosenzweig, Zih-Jie Shen, Tanya Schild, Martin A. Rivas, Ekrem E. Er, Dylan R. McNally, Anders P. Mutvei, Julie Han, Yi-Hung Ou, Paola Cavaliere, Edouard Mullarky, Michal Nagiec, Sejeong Shin, Sang-Oh Yoon, Noah Dephoure, Joan Massagué, Ari M. MelnickSummaryMetastasis 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research