期刊
CELL REPORTS
卷 19, 期 4, 页码 875-889出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.078
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类别
资金
- NIH [5U01 CA141508, U01 CA168394, R01ES024995, U01 HG007912, CA016672, GM110174, CA196539]
- NCI [1K99CA160578, R00CA160578]
- Cancer Prevention and Research Institute of Texas [R1204]
- National Science Foundation [1254200]
- Center for Cancer Epigenetics at MDACC
- Charles A. King postdoctoral fellowship
- Alfred P. Sloan fellowship
- California Institute for Regenerative Medicine Training Grant [TG2-01169]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Training Program
- Direct For Biological Sciences [1254200] Funding Source: National Science Foundation
- Div Of Biological Infrastructure [1254200] Funding Source: National Science Foundation
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.
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