GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE282nnn/GSE282031/primary200OKTranscriptomicsHomo sapiens Genome binding/occupancy profiling by high throughput sequencing OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282031GEOGSEfalseBRD4 O-GlcNAcylation attenuates phase separation to regulate transcriptionBRD4 undergoes liquid-liquid phase separation (LLPS) at super-enhancers (SEs) to facilitate gene control. However, the regulatory mechanisms and transcriptional consequences of BRD4 condensation remain elusive. Here, we show that the BRD4 C-terminal intrinsically disordered region (IDR) is a primary interacting region for O-GlcNAc transferase (OGT), enabling O-GlcNAc modifications at 12 potential sites. O-GlcNAcylation attenuates BRD4 LLPS, leading to small puncta and increased fluidity, which significantly declines occupancy and transcription at SEs. We further demonstrate that loss of O-GlcNAcylation on BRD4 led to elevated gene expression relating to cell cycle and DNA damage, allowing cells less sensitive to DNA damage and promoting faster growth. Therefore, we identify an O-GlcNAc–mediated regulatory mechanism for BRD4 LLPS that governs gene control at SEs, showcasing how O-GlcNAc modifications can influence transcriptional activities at SEs through a phase separation model.2026/07/29GSE282031GSM8634662GSM9787157GSM9787156GSM8634660GSM8634661GSM8634644GSM9787153GSM9787152GSM8634645GSM9787155GSM8634642GSM8634643GSM9787154GSM8634648GSM8634649GSM8634646GSM8634647GSM9038251GSM9038250GSM9038253GSM9038252GSM9787151GSM9787150GSM8634651GSM8634652GSM8634650GSM8634655GSM9038248GSM9038247GSM8634656GSM8634653GSM9038249GSM8634654GSM8634659GSM8634657GSM9038246GSM8634658GSM97871492467629480282031Homo sapiens