Region-specific alteration of histone modification by LSD1 inhibitor conjugated with pyrrole-imidazole polyamide.

ABSTRACT: Epigenome regulates gene expression to determine cell fate, and accumulation of epigenomic aberrations leads to diseases, including cancer. NCD38 inhibits lysine-specific demethylase-1 (LSD1), a histone demethylase targeting H3K4me1 and H3K4me2, but not H3K4me3. In this study, we conjugated NCD38 with a potent small molecule called pyrrole (Py) imidazole (Im) polyamide, to analyze whether targets of the inhibitor could be regulated in a sequence-specific manner. We synthesized two conjugates using β-Ala (β) as a linker, i.e., NCD38-β-β-Py-Py-Py-Py (NCD38-β₂P₄) recognizing WWWWWW sequence, and NCD38-β-β-Py-Im-Py-Py (NCD38-β₂PIPP) recognizing WWCGWW sequence. When RKO cells were treated with NCD38, H3K4me2 levels increased in 103 regions with significant acti

SUBMITTER: Alagarswamy K 

PROVIDER: S-EPMC6047668 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature