HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells.

ABSTRACT:

Background

Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. Therefore, elucidating the mechanisms by which HDACi trigger differentiation, cell cycle arrest, or apoptosis of cancer cells could inform development of more targeted therapies. We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process.

Results

We identified several thousand specific regulatory elements [~10 % of total DNase I-hypersensitive (DHS) sites] that become significantly mor

SUBMITTER: Frank CL 

PROVIDER: S-EPMC4833939 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature