Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Jun 9

PMID 26051178

Citations 115

Authors

Chiara Vardabasso

Alexandre Gaspar-Maia

Dan Hasson

Sebastian Punzeler

David Valle-Garcia

Tobias Straub

Eva C Keilhauer

Thomas Strub

Joanna Dong

Taniya Panda

Chi-Yeh Chung

Jonathan L Yao

Rajendra Singh

Miguel F Segura

Barbara Fontanals-Cirera

Amit Verma

Matthias Mann

Eva Hernando

Sandra B Hake

Emily Bernstein

Affiliations

Soon will be listed here.

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. We further 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 targeted therapies. 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.

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