Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes.

ABSTRACT:

Purpose

Abnormal DNA CpG island hypermethylation and transcriptionally repressive histone modifications are associated with the aberrant silencing of tumor suppressor genes. Lysine methylation is a dynamic, enzymatically controlled process. Lysine-specific demethylase 1 (LSD1) has recently been identified as a histone lysine demethylase. LSD1 specifically catalyzes demethylation of mono- and dimethyl-lysine 4 of histone 3 (H3K4), key positive chromatin marks associated with transcriptional activation. We hypothesized that a novel class of oligoamine analogues would effectively inhibit LSD1 and thus cause the reexpression of aberrantly silenced genes.

Experimental design

Human colorectal cancer cells were treated with the oligoamines and changes in mono- and dimethyl-H3K4 and

SUBMITTER: Huang Y 

PROVIDER: S-EPMC2927136 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature