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  Histone Variant H2AZ2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma

Vardabasso, C., Gaspar-Maia, A., Hasson, D., Pünzeler, S., Valle-Garcia, D., Straub, T., et al. (2015). Histone Variant H2AZ2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma. MOLECULAR CELL, 59(1), 75-88. doi:10.1016/j.molcel.2015.05.009.

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 Creators:
Vardabasso, Chiara1, Author
Gaspar-Maia, Alexandre1, Author
Hasson, Dan1, Author
Pünzeler, Sebastian1, Author
Valle-Garcia, David1, Author
Straub, Tobias1, Author
Keilhauer, Eva C.2, Author              
Strub, Thomas1, Author
Dong, Joanna1, Author
Panda, Taniya1, Author
Chung, Chi-Yeh1, Author
Yao, Jonathan L.1, Author
Singh, Rajendra1, Author
Segura, Miguel F.1, Author
Fontanals-Cirera, Barbara1, Author
Verma, Amit1, Author
Mann, Matthias2, Author              
Hernando, Eva1, Author
Hake, Sandra B.1, Author
Bernstein, Emily1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: GENE-EXPRESSION; CELL-CYCLE; H2A.Z; CHROMATIN; PROGRESSION; IDENTIFICATION; NUCLEOSOMES; METASTASIS; CANCER; TRANSCRIPTION
 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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Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: MOLECULAR CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 59 (1) Sequence Number: - Start / End Page: 75 - 88 Identifier: ISSN: 1097-2765