Omics · study · 2026
Regulation of lineage reprogramming by dynamic chromatin SUMOylation (RNA-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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311975 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311975 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1372010 ncbi.nlm.nih.gov/bioproject/PRJNA1372010 ↗
project · from NCBI GEO
- PubMed 42201422 pubmed.ncbi.nlm.nih.gov/42201422 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Mass spectrometry 65% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE311975 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |