Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.

ABSTRACT: Obesity-induced β cell dysfunction contributes to the onset of type 2 diabetes. Nevertheless, elucidating epigenetic mechanisms underlying islet dysfunction at single cell level remains challenging. Here we profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets from lean or obese mice. Our study identifies distinct gene signatures and enhancer states correlating with β cell dysfunction trajectory. Intriguingly, while many metabolic stress-induced genes exhibit concordant changes in both H3K4me1 and H3K27ac at their enhancers, expression changes of specific subsets are solely attributable to either H3K4me1 or H3K27ac dynamics. Remarkably, a subset of H3K4me1⁺H3K27ac^- primed enhancers prevalent in lean β cells and occupied by FoxA2 are largely

SUBMITTER: Wang L 

PROVIDER: S-EPMC11522703 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature