GEOTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311975GEOGSEfalseRegulation of lineage reprogramming by dynamic chromatin SUMOylation (RNA-seq)SUMOylation has emerged as a key regulator of chromatin and transcription, yet its contribution to lineage reprogramming remains unclear. To explore how chromatin SUMOylation influences cellular plasticity, we studied CEBPA-driven lineage reprogramming of human leukemic B-cells into macrophage-like cells. By integrating ChIP-seq, ATAC-seq, RNA-seq and chromatin-directed proteomics, we mapped the chromatin landscape and transcriptomic changes during early reprogramming. Lineage conversion triggered a dynamic rise in SUMO2/3 chromatin occupancy at CEBPA-bound sites, revealing a coordinated regulatory mechanism. Proteomic profiling of SUMO2/3- and CEBPA-associated chromatin uncovered extensive convergence and enrichment of differentiation-related transcription factors, chromatin remodelers and coregulators. Among these, NCOA3 displayed markedly increased SUMO2/3 association upon lineage conversion. NCOA3 co-occupied CEBPA- and SUMO2/3-bound chromatin regions, implying a SUMOylation-supported coregulatory role in lineage reprogramming. Pharmacological inhibition of SUMOylation using ML-792 (SUMOi) selectively enhanced CEBPA chromatin occupancy and chromatin accessibility, altered the CEBPA association of proteins, and modified NCOA3 binding dynamics. SUMOi also reshaped gene expression, promoting loss of B-cell identity and activation of macrophage-associated programs, including lipid metabolism. Collectively, our findings highlight chromatin SUMOylation as a dynamic and context-dependent modifier that fine-tunes lineage transitions, with implications for chromatin biology and therapeutic modulation of cell identity.2026/05/27GSE311975GSM9335469GSM9335502GSM9335503GSM9335500GSM9335489GSM9335467GSM9335501GSM9335468GSM9335504GSM9335505GSM9335483GSM9335484GSM9335481GSM9335482GSM9335487GSM9335465GSM9335466GSM9335488GSM9335485GSM9335486GSM9335464GSM9335480GSM9335478GSM9335479GSM9335494GSM9335472GSM9335495GSM9335473GSM9335492GSM9335470GSM9335471GSM9335493GSM9335498GSM9335476GSM9335477GSM9335499GSM9335474GSM9335496GSM9335497GSM9335475GSM9335490GSM933549111154311975Homo sapiens