@article{f80df9f17d374dd0bdc04878b1257585,
title = "Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma",
abstract = "Histone variants are emerging as key regulatory molecules in cancer. We report a unique role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z-interacting protein, levels of which are also elevated in melanoma. Wefurther demonstrate that H2A.Z.2-regulated genes are bound by BRD2 and E2F1 in an H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targetedtherapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies.",
author = "Chiara Vardabasso and Alexandre Gaspar-Maia and Dan Hasson and Sebastian P{\"u}nzeler and David Valle-Garcia and Tobias Straub and Keilhauer, {Eva C.} and Thomas Strub and Joanna Dong and Taniya Panda and Chung, {Chi Yeh} and Yao, {Jonathan L.} and Rajendra Singh and Segura, {Miguel F.} and Barbara Fontanals-Cirera and Amit Verma and Matthias Mann and Eva Hernando and Hake, {Sandra B.} and Emily Bernstein",
note = "Funding Information: The authors are grateful for assistance and reagents provided by Luis Duarte, Avnish Kapoor, Nicholas Mills, Clemens B{\"o}nisch, Pauline Rimmele, Danielle Martinez, and the laboratories of Robert Fisher, Stuart Aaronson, Ramon Parsons, and Jay Bradner. We thank Cristina Montagna and Jidong Shan at Molecular Cytogenetic Core at Albert Einstein College of Medicine; Genomics Core Facility at Mount Sinai; Avi Ma{\textquoteright}ayan for statistical support; Robert Phelps, Madelaine Haddican, Shelbi Jim On, and Giselle Singer for assistance with benign nevi collection; and Mark Lebwohl for his support. Funding was supported by a Melanoma Research Development Award (Mount Sinai) to C.V.; DOD BCRP Postdoctoral fellowship (W81XWH-11-1-0018) and NYSCF Druckenmiller Fellowship to A.G.-M.; graduate fellowship from CONACyT (239663) to D.V.-G.; International Max Planck Research School for Life Science (IMPRS-LS) to S.P.; Bundesministerium f{\"u}r Bildung und Forschung (FKZ01GS0861, DiGtoP consortium) to M.M.; DOD Collaborative Awards CA093471 (W81XWH-10-1-080), 1R01CA155234, and 1R01CA163891 to E.H.; Deutsche Forschungsgemeinschaft through the Collaborative Research Center SFB 1064 (project A10 to S.B.H. and project Z04 to T.S.); HA 5437/4-1 and the Center for Integrated Protein Science Munich (CIPSM) to S.B.H.; Worldwide Cancer Research, Hirschl/Weill-CaulierResearch Award; and NCI/NIH R01CA154683 to E.B. We dedicate this study in memory of Estela Medrano. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
doi = "10.1016/j.molcel.2015.05.009",
language = "English",
volume = "59",
pages = "75--88",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}