MeCP2 binding and genome-lamina reorganization precede long neuronal gene

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.