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MeCP2 binding and genome-lamina reorganization precede long neuronal gene

ABSTRACT: During corticogenesis, neural gene expression is tightly coordinated by changes in chromatin state and epigenetic regulation. However, the role of spatial genome organization—particularly interactions with the nuclear lamina—during these developmental programs remains poorly understood. Here, we combined in utero electroporation with scDam&T-seq to jointly profile genome-lamina contacts and transcriptomes in single cells of the mouse embryonic cortex. We uncover a large cohort of long, neuronal function-related genes that undergo spatial genome-lamina repositioning during neurogenesis. Notably, detachment of these genes frequently precedes transcriptional activation, positioning lamina disengagement as an early gene regulatory event. We further identify the methyl CpG binding protein 2 (MeCP2)—mutated in Rett syndrome—as a candidate mediator of this process. MeCP2 binds lamina-associated, hydroxymethylated long genes before their repositioning, suggesting that MeCP2 may prime genome-lamina reorganization. These findings suggest a link between prevalent genome-lamina reorganization and MeCP2 regulation to ensure proper spatiotemporal activation of neuronal genes during corticogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE300282 | GEO | 2026/07/15

REPOSITORIES: GEO

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