@article{873dacbe79f0433e91a148f8dc878869,
title = "Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression",
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.",
keywords = "CBP, ChIP-seq, DUSP5, HDAC, chromatin state, epigenome, histone modifications, melanoma",
author = "Petko Fiziev and Akdemir, {Kadir C.} and Miller, {John P.} and Keung, {Emily Z.} and Samant, {Neha S.} and Sneha Sharma and Natale, {Christopher A.} and Terranova, {Christopher J.} and Mayinuer Maitituoheti and Amin, {Samirkumar B.} and Emmanuel Martinez-Ledesma and Mayura Dhamdhere and Axelrad, {Jacob B.} and Amiksha Shah and Cheng, {Christine S.} and Harshad Mahadeshwar and Sahil Seth and Barton, {Michelle C.} and Alexei Protopopov and Tsai, {Kenneth Y.} and Davies, {Michael A.} and Garcia, {Benjamin A.} and Ido Amit and Lynda Chin and Jason Ernst and Kunal Rai",
note = "Funding Information: We thank Siavash Kurdistani, Sharmistha Sarkar, Yonathan Lissanu Deribe, Ian R. Watson, and Lawrence Kwong for useful discussions or comments on the manuscript. We thank Marcus Coyle, Curtis Gumbs, and SMF core at MDACC for sequencing support. The work described in this article was supported by the NIH (grants 5U01 CA141508 and U01 CA168394 to L.C.; grants R01ES024995 and U01 HG007912 to J. E.; grant CA016672 to SMF Core; grants GM110174 and CA196539 to B.A.G.), NCI (grants 1K99CA160578 and R00CA160578 to K.R.), Cancer Prevention and Research Institute of Texas (grant R1204 to L.C.), National Science Foundation (grant 1254200 to J.E.), and Center for Cancer Epigenetics at MDACC (K.R.). The following fellowship support is acknowledged: Charles A. King postdoctoral fellowship (to K.R.), Alfred P. Sloan fellowship (to J.E.), California Institute for Regenerative Medicine Training Grant TG2-01169 (to P.F.), and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Training Program (P.F.). Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = apr,
day = "25",
doi = "10.1016/j.celrep.2017.03.078",
language = "English (US)",
volume = "19",
pages = "875--889",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}