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Allelic topological centering by transcription factors drives oncogenic multi-enhancer transcriptional regulation [ChIP-seq]

GSE293334 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 60 samples Submitted 2025/11/13 Platform GPL24676
Summary
Multiple enhancers, often located across vast genomic distances, regulate key genes in cancer. However, how organization of chromatin topology at individual allele enables cancer type-restricted multi-enhancer gene regulation remains unclear. Using acute protein degradation and time-course population-average chromatin conformation capture in lymphoma, we found that the B-cell lineage-determining transcription factor EBF1 preferentially positions multiple enhancers at loci containing sparsely distributed genes essential for B-cell identity and oncogenesis. Our time-resolved sub-diffraction optical tracing of chromatin architecture of over 100,000 alleles further revealed diverse topological conformations that facilitate multi-enhancer interactions in individual lymphoma cells. Mechanistically, we found that positioning of enhancers at the topological center of the allele is required for their interactions with the target promoter, with EBF1 serving as a barrier to the loop extruding cohesin on the enhancers. These findings, which we demonstrate their generalizability to the T-cell lineage-determining transcription factor TCF1 in T-cell leukemia, suggest that lineage-determining transcription factors establish local radial positioning of enhancers and promoters to enable multi-enhancer regulation of key genes in cancer.
Published in
Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation
Zhou Y, Jay A, Burget N et al. · Nature cell biology 2026 · PMID 41331087 · doi:10.1038/s41556-025-01827-2
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE293334_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 60 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1244142 and SRA study SRP575254. Searching any of these in the dataset finder brings you back here.

Study design
20 conditions, mostly in duplicate
Granta519EBF1KIcl27,0hr,H3K27acChIP, ×2 Granta519EBF1KIcl27,0hr,H3K4me1ChIP, ×2 Granta519EBF1KIcl27,0hr,H3K27me3ChIP, ×2 Granta519EBF1KIcl27,6hr,H3K27acChIP, ×2 Granta519EBF1KIcl27,6hr,H3K4me1ChIP, ×2 Granta519EBF1KIcl27,6hr,H3K27me3ChIP, ×2 Granta519EBF1KIcl27,24hr,H3K27acChIP, ×2 Granta519EBF1KIcl27,24hr,H3K4me1ChIP, ×2 +12 more

Supports a between-group comparison across 40 samples.

20 replicated groups read from the first 40 of 60 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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