ArticleCell reports2017
Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression.
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Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
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Who cites it
53 citing papers in PubMed.
- Functional characterization of the 9q34.13 locus identifies RAPGEF1 as a candidate gene modulating risk for melanoma and nevi via RAS activation.American journal of human genetics · 2026Article
- Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability.PLoS computational biology · 2026Article
- A high-penetrance intergenic variant at 9p21 confers melanoma susceptibility.Research square · 2026Article
- Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability.bioRxiv : the preprint server for biology · 2026Article
- Functional characterization of the 9q34.13 locus identifiesbioRxiv : the preprint server for biology · 2026Article
- Epigenetic modifiers to enhance the efficacy of immune checkpoint inhibitors for the treatment of melanoma.Translational oncology · 2025Review
- Combinatorial DNMTs and EZH2 inhibition reprograms the H3K27me3 and DNAme-mediated onco-epigenome to suppress multiple myeloma proliferation.Scientific reports · 2025Article
- Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets.American journal of human genetics · 2025Article
- Epigenetic Therapies in Melanoma-Targeting DNA Methylation and Histone Modification.Biomedicines · 2025Review
- H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric Gliomas.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive genome annotation of the model ciliate Tetrahymena thermophila by in-depth epigenetic and transcriptomic profiling.Nucleic acids research · 2025Article
- Understanding relationships between epigenetic marks and their application to robust assignment of chromatin states.Briefings in bioinformatics · 2024Article
- CDK9 inhibitors for the treatment of solid tumors.Biochemical pharmacology · 2024Review
- Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.Genome biology · 2024Article
- Deciphering the genetics and mechanisms of predisposition to multiple myeloma.Nature communications · 2024Article
- Targeted DNA Methylation Editing Using an All-in-One System Establishes Paradoxical Activation ofCancers · 2024Article
- The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma.The Journal of clinical investigation · 2024Article
- Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified mCancer communications (London, England) · 2023Article
- MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.Communications biology · 2023Article
- Rapid Single-Pot Assembly of Modular Chromatin Proteins for Epigenetic Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
26 authors.
Petko FizievBioinformatics Interdepartmental Program, University of California, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
Kadir C AkdemirDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
John P MillerDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Emily Z KeungDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Neha S SamantDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Sneha SharmaDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Christopher A NataleDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher J TerranovaDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Mayinuer MaitituohetiDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Samirkumar B AminDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Emmanuel Martinez-LedesmaDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Mayura DhamdhereDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jacob B AxelradDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Amiksha ShahDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Christine S ChengBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Boston University, Boston, MA 02215, USA.
Harshad MahadeshwarDivision of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Sahil SethDivision of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Michelle C BartonDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Alexei ProtopopovDivision of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Kenneth Y TsaiDivision of Internal Medicine, Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Michael A DaviesDivision of Cancer Medicine, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Benjamin A GarciaDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ido AmitWeizmann Institute of Science, Rehovot 761001, Israel.
Lynda ChinDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Division of Cancer Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Institute for Health Transformation, The University of Texas System, Austin, TX 78701, USA. Electronic address: lchin@utsystem.edu.
Jason ErnstBioinformatics Interdepartmental Program, University of California, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Department of Computer Science, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA. Electronic address: jason.ernst@ucla.edu.
Kunal RaiDivision of Cancer Medicine, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: krai@mdanderson.org.
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MShared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6MTRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2M"Ribonomics" of Gene Regulation to predict Innate Immune ResponsesU01HG007912 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L, HOFFMANN, ALEXANDER · 2015 to 2017
$5.8MBiological annotation of TCGA dataU01CA168394 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MILLS, GORDON B. · 2012 to 2016
$4.7MUses of GEM models for Translational Cancer ResearchU01CA141508 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHIN, LYNDA · 2009 to 2013
$3.9MIntegrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6MUnderstanding the Role of Combinatorial Histone PTM PatternsR01GM110174 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2014 to 2017
$1.3MEpigenetics of Melanoma MetastasisR00CA160578 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2015 to 2017
$747kEpigenomic control of RNA splicingR01ES024995 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER, XING, YI · 2014 to 2015
$616kEpigenetics of Melanoma MetastasisK99CA160578 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2011 to 2012
$284kNCI NIH HHS K99 CA160578NCI NIH HHS P01 CA196539NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA160578NCI NIH HHS T32 CA009599NCI NIH HHS U01 CA141508NCI NIH HHS U01 CA168394NCI NIH HHS U01 CA217842NHGRI NIH HHS U01 HG007912NIEHS NIH HHS R01 ES024995NIGMS NIH HHS R01 GM110174
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.
Indexed as
EpigenomicsAcetylationCell LineCell ProliferationChromatinChromatin ImmunoprecipitationDisease-Free SurvivalHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansHydroxamic AcidsKaplan-Meier EstimateMelanomaPrincipal Component AnalysisPTEN PhosphohydrolaseChromatinHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic AcidsPTEN PhosphohydrolasePTEN protein, humanRNA, Small InterferingVorinostatCBPChIP-seqchromatin stateDUSP5epigenomeHDAChistone modificationsmelanoma
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