Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells

Abstract

KANSL2 is a subunit of the non-specific lethal (NSL) chromatin-modifying complex associated with glioblastoma (GBM) progression, but the intrinsic role of KANSL2 in GBM cells is poorly understood. By analyzing TCGA-GBM and GTEx datasets, we found that KANSL2 is upregulated in GBM and positively correlates with genes involved in ribosome biogenesis. Immunofluorescence and cell cycle analyses reveal a dynamic nuclear distribution, with KANSL2 becoming enriched in nucleoli mainly during G1/early S and G2 phases. Overexpression of KANSL2 increases 45S pre-rRNA and 28S rRNA levels, whereas its silencing reduces rRNA expression and histone H4 acetylation at lysines 5 and 8 within rDNA promoters. RNA-seq of patient-derived GBM spheroids confirms a global downregulation of ribosome biogenesis genes upon silencing of KANSL2. Together, these findings identify KANSL2 as a nuclear factor that transiently associates with nucleoli to promote rRNA transcription and ribosome biogenesis, supporting the biosynthetic and proliferative capacity of glioblastoma cells.