Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance

Zhiquan Wang, Rentian Wu, Qian Nie, Kelly J. Bouchonville, Robert B. Diasio, Steven M. Offer

Research output: Contribution to journalArticlepeer-review


The long-term effectiveness of targeted cancer therapies is limited by the development of resistance. Although epigenetic reprogramming has been implicated in resistance, the mechanisms remain elusive. Herein, we demonstrate that increased chromatin accessibility is involved in adaptive BRAF inhibitor (BRAFi)-resistance in melanoma cells. We observed loss of chromatin assembly factor 1 (CAF-1) and its related histone H3 lysine 9 trimethylation (H3K9me3) with adaptive BRAFi resistance. We further showed that depletion of CAF-1 provides chromatin plasticity for effective reprogramming by AP1 components to promote BRAFi resistance. Our data suggest that therapeutic approaches to restore H3K9me3 levels may compensate for the loss of CAF-1 and, in turn, suppress resistance to BRAF inhibitors.

Original languageEnglish (US)
Pages (from-to)15-22
Number of pages8
JournalJournal of the National Cancer Center
Issue number1
StatePublished - Mar 2021


  • Adaptive drug resistance
  • BRAF inhibitor
  • Chromatin assembly factor 1
  • Epigenetic reprogramming
  • H3K9me3
  • Nucleosome assembly
  • Targeted therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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