Persistent chromatin loops shape gene expression plasticity upon stimulation and restimulation of human neurons.

ABSTRACT: Persistent molecular correlates of long-term memory storage remain an open question. Here, we stimulate and re-stimulate human neurons and use multi-modal single-nucleus technologies to query DNA methylation, higher-order chromatin folding, and gene expression. We find enduring traces of activity-gained and activity-lost chromatin loops. Genes anchoring persistent activity-gained loops exhibit activity-upregulated expression, whereas persistent activity-lost loops anchor activity-downregulated genes that remain repressed five days post-stimulation. CTCF-bound looped enhancers and promoters are refractory to activity-dynamic DNA methylation. Looped enhancers bound by CTCF can exhibit memory of activity-induced histone modifications and persistent expression of activity-upregulated genes. Up

SUBMITTER: Waldman AJ 

PROVIDER: S-EPMC12621786 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature