An epigenetic small molecule screen to target abnormal nuclear morphology in human cells.

ABSTRACT: Irregular nuclear shapes are a hallmark of human cancers. Recent studies suggest that alterations to chromatin regulators may cause irregular nuclear morphologies. Here we screened an epigenetic small molecule library consisting of 145 compounds against chromatin regulators for their ability to revert abnormal nuclear shapes that were induced by gene knockdown in noncancerous MCF10A human mammary breast epithelial cells. We leveraged a previously validated quantitative Fourier approach to quantify the elliptical Fourier coefficient (EFC ratio) as a measure of nuclear irregularities, which allowed us to perform rigorous statistical analyses of screening data. Top hit compounds fell into three major mode of action categories, targeting three separate epigenetic modulation routes: 1) histone

SUBMITTER: Atanasova KR 

PROVIDER: S-EPMC9265153 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature