Lamin B1 regulates RNA splicing factor expression by modulating the spatial positioning and chromatin interactions of the ETS1 gene locus.

Abstract

Lamin B1, a crucial component of the nuclear lamina, plays a pivotal role in chromatin organization and transcriptional regulation in eukaryotic cells. While recent studies have highlighted the connection between Lamin B1 and RNA splicing regulation, the precise molecular mechanisms remain elusive. In this study, we demonstrate that Lamin B1 depletion leads to a global reduction in splicing factor expression, as evidenced by analysis of multiple RNA-seq datasets. Motif analysis suggests that members of the ETS transcription factor family likely bind to the promoter regions of these splicing factors. Further analysis using transcription factor databases and ChIP-seq data identified ETS1 as a key regulator of splicing factor expression. Hi-C sequencing revealed that the loss of Lamin B1 disrupts inter-LAD chromatin interactions near the ETS1 gene locus, resulting in its downregulation. These findings suggest that Lamin B1 indirectly regulates RNA splicing by sustaining proper ETS1 expression, uncovering a novel link between nuclear architecture, gene regulation, and RNA splicing.