Dynamic incorporation of histone H3 variants into chromatin is essential for acquisition of aggressive traits and metastatic colonization Journal Article
| Authors: | Gomes, A. P.; Ilter, D.; Low, V.; Rosenzweig, A.; Shen, Z. J.; Schild, T.; Rivas, M. A.; Er, E. E.; McNally, D. R.; Mutvei, A. P.; Han, J.; Ou, Y. H.; Cavaliere, P.; Mullarky, E.; Nagiec, M.; Shin, S.; Yoon, S. O.; Dephoure, N.; Massagué, J.; Melnick, A. M.; Cantley, L. C.; Tyler, J. K.; Blenis, J. |
| Article Title: | Dynamic incorporation of histone H3 variants into chromatin is essential for acquisition of aggressive traits and metastatic colonization |
| 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. © 2019 Elsevier Inc. Gomes et al. reveal metastatic stimuli reduce histone H3.1/H3.2 deposition on chromatin by suppressing the CAF-1 complex in breast and NSCLC cancer cells, leading to increased incorporation of non-canonical histone H3.3, which in turn induces chromatin remodeling and expression of metastatic genes. © 2019 Elsevier Inc. |
| Keywords: | metastasis; epigenetics; tumor progression; histone chaperones; chromatin remodeling; hira; histone h3.3; caf-1 complex |
| Journal Title: | Cancer Cell |
| Volume: | 36 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2019-10-14 |
| Start Page: | 402 |
| End Page: | 417.e13 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2019.08.006 |
| PUBMED: | 31564638 |
| PROVIDER: | scopus |
| PMCID: | PMC6801101 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work