February 6, 2020

New tool probes gene regulation

Vanderbilt biochemists got unexpected results when they used their new approach to explore the role of DNA methylation in gene regulation.

DNA methylation (DNAme) is a modification of the genome — an epigenetic “mark” — that is required for proper cellular differentiation. It has been implicated in the regulation of gene expression, but its role in the stepwise process of gene regulation is poorly understood.

Emily Hodges, PhD, graduate student Kelly Barnett and colleagues have developed a new tool, ATAC-Me, to simultaneously measure DNAme and chromatin accessibility in the same population of DNA molecules. The researchers used ATAC-Me to probe the differentiation of white blood cells from monocytes to macrophages.

They identified waves of chromatin accessibility occurring rapidly across thousands of enhancers (regions of DNA involved in regulating gene expression). They also found unexpected prolonged methylation states at a majority of the sites, challenging the long-held belief that DNA methylation is a barrier to gene activation.

The studies, reported in Molecular Cell, highlight the value of ATAC-Me for exploring the role of DNA methylation in gene regulation.

This research was supported by grants from the National Institutes of Health (CA184308, HD007502, HG007650).