Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression.
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Abstract | The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression. |
Year of Publication | 2017
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Journal | Cell Rep
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Volume | 19
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Issue | 4
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Pages | 875-889
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Date Published | 2017 04 25
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ISSN | 2211-1247
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DOI | 10.1016/j.celrep.2017.03.078
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PubMed ID | 28445736
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PubMed Central ID | PMC5473172
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Grant list | R01 ES024995 / ES / NIEHS NIH HHS / United States
R00 CA160578 / CA / NCI NIH HHS / United States
P01 CA196539 / CA / NCI NIH HHS / United States
U01 CA168394 / CA / NCI NIH HHS / United States
R01 GM110174 / GM / NIGMS NIH HHS / United States
K99 CA160578 / CA / NCI NIH HHS / United States
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