GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327055/primaryOK200OtherMus musculus Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencingOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327055GEOGSEfalseLncRNA Gas5 directs SUV39H2 to establish heterochromatin and maintain genome stabilityConstitutive heterochromatin, characterized by histone H3 lysine 9 trimethylation (H3K9me3), is essential for genome stability, pluripotency, and developmental fidelity. While the SUV39H histone methyltransferases catalyze H3K9me3 deposition, their locus-specific targeting mechanisms remain unclear. Here, via RNA depletion or RNA-binding affinity mutation, we establish that RNA binding is indispensable for SUV39H2 recruitment to chromatin and H3K9me3 maintenance in mouse embryonic stem cells (ESCs). Through RNA immunoprecipitation sequencing (RIP-Seq) and functional validation, we identify the long non-coding RNA Gas5 as a specific SUV39H2 interactor. Depletion of Gas5 or disruption of the SUV39H2–RNA interaction leads to the loss of self-renewal capacity of ESCs, abolishes H3K9me3 enrichment, along with profound genomic instability, mitotic errors, and γH2AX foci accumulation. These findings reveal a critical lncRNA-dependent mechanism governing the SUV39H2–H3K9me3 axis, which directly couples RNA metabolism to the preservation of pluripotency and genome integrity in stem cells.2026/04/08GSE327055GSM9647218GSM9647207GSM9647208GSM9647209GSM9647210GSM9647211GSM9647212GSM9647213GSM9647214GSM9647215GSM9647205GSM9647216GSM9647217GSM96472062110321626327055Mus musculus