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Omics · study · 2026

Regulation of lineage reprogramming by dynamic chromatin SUMOylation (ChIP-seq)

Listed in NCBI GEO

SUMOylation has emerged as a key regulator of chromatin and transcription, yet its contribution to lineage reprogramming remains unclear.

Description

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.

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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.

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Life Sciences
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Genetics 72% · Mass spectrometry 65% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
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NCBI GEOGSE31197115 d agoJSON v1
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