CHD4 and NKX2.2 Cooperate to Regulate β-Cell Function by Repressing Non-β-Cell Gene Programs.

Sarbaugh, Dylan; Oliveira, Thais Gaia; Guney, Michelle A; Casey, McKenna R; Hoelscher, Victoria M; Hill, Christopher J; Michel, Cole R; Wells, Kristen L et al. · Diabetes · 2026

basic_science · Level V

Where this comes from

Abstract

NKX2.2 interacts with the nucleosome remodeling and deacetylase complex through its interaction with chromodomain helicase DNA-binding protein 4 (CHD4). Deletion of CHD4 from developing pancreatic β-cells in mice causes diabetes due to a loss of islet integrity, disrupted calcium signaling, and impaired insulin secretion. β-cells lacking CHD4 inappropriately upregulate the G protein-activated inward rectifier potassium channel 4 (GIRK4) potassium channel; inhibition of GIRK4 rescues the insulin secretion defect.