Pluto Biosciences, Inc

GSE157375: The inner nuclear membrane protein LEMD2 and the chromatin organizer SATB2 regulate overlapping gene-sets in primary cortical neurons

Bulk RNA sequencing

SATB2, encoding a nuclear chromosomal scaffolding protein, is a schizophrenia risk gene and genetically associated with human intelligence. How SATB2 affects cognition at molecular level is currently unknown. Our data suggest that interactions between SATB2 and the inner nuclear membrane protein LEMD2 orchestrate gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology. We show that LEMD2, a candidate component of the A-heterochromatin tether, binds to SATB2 and the two proteins exert overlapping cellular functions. SATB2 is essential for neuronal activity-triggered nuclear envelope plasticity, which requires LEMD2 as well as the ESCRT-III/VPS4 complex. LEMD2-depletion in cortical neurons, like SATB2 ablation, affects the expression of multiple neuronal activity-regulated genes. The gene-sets regulated by LEMD2 and SATB2 significantly overlap and the LEMD2 gene-set is enriched for SATB2-bound genes. In human genetic data, LEMD2-regulated genes are enriched for loss-of-function mutations reported in autism, intellectual disability and schizophrenia and are, like SATB2-regulated genes, associated with cognitive function. SOURCE: Galina Apostolova ( - Dechant Lab Medical University Innsbruck

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