TitleDynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization.
Publication TypeJournal Article
Year of Publication2019
AuthorsGomes, Ana P., Ilter Didem, Low Vivien, Rosenzweig Adam, Shen Zih-Jie, Schild Tanya, Rivas Martín A., Er Ekrem E., McNally Dylan R., Mutvei Anders P., Han Julie, Ou Yi-Hung, Cavaliere Paola, Mullarky Edouard, Nagiec Michal, Shin Sejeong, Yoon Sang-Oh, Dephoure Noah, Massagué Joan, Melnick Ari M., Cantley Lewis C., Tyler Jessica K., and Blenis John
JournalCancer Cell
Volume36
Issue4
Pagination402-417.e13
Date Published2019 10 14
ISSN1878-3686
KeywordsAnimals, Carcinogenesis, Carcinoma, Cell Line, Tumor, Chromatin, Chromatin Assembly Factor-1, Disease Progression, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Histones, Humans, Male, Mice, Neoplasm Metastasis, Promoter Regions, Genetic, RNA-Seq, Transcription Factors, Xenograft Model Antitumor Assays
Abstract

<p>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.</p>

DOI10.1016/j.ccell.2019.08.006
Alternate JournalCancer Cell
PubMed ID31564638
PubMed Central IDPMC6801101
Grant ListR35 CA220499 / CA / NCI NIH HHS / United States
R01 CA046595 / CA / NCI NIH HHS / United States
K99 CA218686 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
T32 GM008539 / GM / NIGMS NIH HHS / United States
R01 CA240835 / CA / NCI NIH HHS / United States
F31 CA220750 / CA / NCI NIH HHS / United States
P01 CA094060 / CA / NCI NIH HHS / United States
R03 CA212562 / CA / NCI NIH HHS / United States