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. TsaiMichael A. Davies, Benjamin A. Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)875-889
Number of pages15
JournalCell Reports
Volume19
Issue number4
DOIs
StatePublished - Apr 25 2017
Externally publishedYes

Keywords

  • CBP
  • ChIP-seq
  • chromatin state
  • DUSP5
  • epigenome
  • HDAC
  • histone modifications
  • melanoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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