Cell Reports (Apr 2017)
Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression
- Petko Fiziev,
- Kadir C. Akdemir,
- John P. Miller,
- Emily Z. Keung,
- Neha S. Samant,
- Sneha Sharma,
- Christopher A. Natale,
- Christopher J. Terranova,
- Mayinuer Maitituoheti,
- Samirkumar B. Amin,
- Emmanuel Martinez-Ledesma,
- Mayura Dhamdhere,
- Jacob B. Axelrad,
- Amiksha Shah,
- Christine S. Cheng,
- Harshad Mahadeshwar,
- Sahil Seth,
- Michelle C. Barton,
- Alexei Protopopov,
- Kenneth Y. Tsai,
- Michael A. Davies,
- Benjamin A. Garcia,
- Ido Amit,
- Lynda Chin,
- Jason Ernst,
- Kunal Rai
Affiliations
- Petko Fiziev
- Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA 90095, USA
- Kadir C. Akdemir
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- John P. Miller
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Emily Z. Keung
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Neha S. Samant
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Sneha Sharma
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Christopher A. Natale
- Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
- Christopher J. Terranova
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Mayinuer Maitituoheti
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Samirkumar B. Amin
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Emmanuel Martinez-Ledesma
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Mayura Dhamdhere
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Jacob B. Axelrad
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Amiksha Shah
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Christine S. Cheng
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Harshad Mahadeshwar
- Division of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Sahil Seth
- Division of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Michelle C. Barton
- Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Alexei Protopopov
- Division of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Kenneth Y. Tsai
- Division of Internal Medicine, Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Michael A. Davies
- Division of Cancer Medicine, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Benjamin A. Garcia
- Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
- Ido Amit
- Weizmann Institute of Science, Rehovot 761001, Israel
- Lynda Chin
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Jason Ernst
- Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA 90095, USA
- Kunal Rai
- Division of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.03.078
- Journal volume & issue
-
Vol. 19,
no. 4
pp. 875 – 889
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
