The Chd4 helicase regulates chromatin accessibility and gene expression critical for β-cell function in vivo.

Pdx1:Chd4 interactions were previously shown to be compromised in β-cells from human donors with type 2 diabetes. β-cell-specific removal of Chd4 impairs insulin secretion and leads to glucose intolerance in mice. Expression of key β-cell functional genes and chromatin accessibility are compromised in Chd4-deficient β-cells. Chromatin remodeling activities enacted by Chd4 are essential for β-cell function under normal physiological conditions.