Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Cell Rep. 2017 Apr 25;19(4):875-889. doi: 10.1016/j.celrep.2017.03.078.


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.

MeSH terms

  • Acetylation
  • Cell Line
  • Cell Proliferation / drug effects
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Disease-Free Survival
  • Epigenomics*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Kaplan-Meier Estimate
  • Melanoma / metabolism
  • Melanoma / mortality
  • Melanoma / pathology
  • PTEN Phosphohydrolase / antagonists & inhibitors
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Principal Component Analysis
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Vorinostat


  • Chromatin
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • RNA, Small Interfering
  • Vorinostat
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Histone Deacetylases