GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311971/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311971GEOGSEfalseRegulation of lineage reprogramming by dynamic chromatin SUMOylation (ChIP-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.2026/05/27GSE311971GSM9335403GSM9335404GSM9335401GSM9335423GSM9335424GSM9335402GSM9335407GSM9335408GSM9335405GSM9335406GSM9335384GSM9335385GSM9335421GSM9335388GSM9335389GSM9335422GSM9335400GSM9335386GSM9335387GSM9335420GSM9335414GSM9335415GSM9335412GSM9335413GSM9335418GSM9335419GSM9335416GSM9335417GSM9335395GSM9335396GSM9335393GSM9335394GSM9335410GSM9335399GSM9335411GSM9335397GSM9335398GSM9335391GSM9335392GSM9335390GSM933540911154311971Homo sapiens