Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs.

ABSTRACT: Epigenetic silencing of tumor suppressor genes (TSGs) is considered a significant event in the progression of cancer. For example, EPB41L3, a potential biomarker in cervical cancer, is often silenced by cancer-specific promoter methylation. Artificial transcription factors (ATFs) are unique tools to re-express such silenced TSGs to functional levels; however, the induced effects are considered transient. Here, we aimed to improve the efficiency and sustainability of gene re-expression using engineered zinc fingers fused to VP64 (ZF-ATFs) or DNA methylation modifiers (ZF-Tet2 or ZF-TDG) and/or by co-treatment with epigenetic drugs [5-aza-2'-deoxycytidine or Trichostatin A (TSA)]. The EPB41L3-ZF effectively bound its methylated endogenous locus, as also confirmed by ChIP-seq. ZF-ATFs reactiv

SUBMITTER: Huisman C 

PROVIDER: S-EPMC4622424 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature