GEO series
Pioneer factors orchestrate tissue-specific cohesin-NIPBL chromatin entry and 3D genome organization [ChIP-seq]
GSE293172
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
68 samples
Submitted 2026/05/07
Platform GPL34284Platform GPL34290Platform GPL24676
Summary
Cohesin complex shapes 3D genome organization by extruding DNA loops, yet the mechanisms underlying its chromatin entry remain poorly understood. Here, we reveal that the cohesin loader NIPBL exhibits highly tissue-specific chromatin binding, in stark contrast to the conserved binding profiles of CTCF and RAD21. We identify pioneer transcription factors (TFs), notably FOXA1, as key mediators of NIPBL recruitment to chromatin. FOXA1 directs NIPBL to intra-TAD regions, enabling symmetric loop extrusion, while factors like ETS1 target NIPBL to TAD boundaries, supporting one-sided extrusion. Rapid depletion of FOXA1 disrupts NIPBL binding and intra-TAD loops, whereas loss of NIPBL impairs both intra-TAD and inter-TAD interactions, highlighting their roles in 3D genome folding. Strikingly, a recurrent FOXA1 mutation (R219S) in prostate cancer redirects NIPBL to TAD boundaries by recognizing a non-canonical motif, fostering a more insulated and tumor-aggressive genome. Evolutionary analysis points to a potential conserved role for TF-NIPBL cooperation in cohesin chromatin entry across species with tissue-specific adaptations. Our findings reveal that pioneer factors orchestrate cohesin loading to shape tissue-specific chromatin accessibility and 3D genome dynamics, a mechanism hijacked in diseases like cancer to rewire gene expression.
Published in
Wang S, Zhang X, Jia T et al.
· Nature genetics 2026
· PMID 42463888
· doi:10.1038/s41588-026-02688-7
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE293172_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 68 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1243290 and SRA study SRP573850. Searching any of these in the dataset finder brings you back here.
Study design
40 conditions, each sampled once — no replicated groups
Supports a case/control comparison: 7 samples read as cases, 8 as controls.
Read from the first 40 of 68 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8877786 22Rv1 cells, H3K27ac, FOXA1_dTAG_0h, rep1 (ChIP)
- GSM8877787 22Rv1 cells, H3K27ac, FOXA1_dTAG_0h, rep2 (ChIP)
- GSM8877788 22Rv1 cells, H3K27ac, FOXA1_dTAG_0h, rep1 (Input)
- GSM8877789 22Rv1 cells, H3K27ac, FOXA1_dTAG_0h, rep2 (Input)
- GSM8877790 22Rv1 cells, H3K27ac, FOXA1_dTAG_24h, rep1 (ChIP)
- GSM8877791 22Rv1 cells, H3K27ac, FOXA1_dTAG_24h, rep2 (ChIP)
- GSM8877792 22Rv1 cells, H3K27ac, FOXA1_dTAG_24h, rep1 (Input)
- GSM8877793 22Rv1 cells, H3K27ac, FOXA1_dTAG_24h, rep2 (Input)
- GSM8877794 22Rv1 cells, NIPBL, FOXA1_dTAG_0h (ChIP)
- GSM8877795 22Rv1 cells, NIPBL, FOXA1_dTAG_0h (Input)
- GSM8877796 22Rv1 cells, NIPBL, FOXA1_dTAG_24h (ChIP)
- GSM8877797 22Rv1 cells, NIPBL, FOXA1_dTAG_24h (Input)
- GSM8877798 22Rv1 cells, CTCF, FOXA1_dTAG_0h (ChIP)
- GSM8877799 22Rv1 cells, CTCF, FOXA1_dTAG_24h (ChIP)
- GSM8877800 22Rv1 cells, RAD21, FOXA1_dTAG_0h (ChIP)
- GSM8877801 22Rv1 cells, RAD21, FOXA1_dTAG_24h (ChIP)
- GSM8877802 22Rv1 cells, Input_CTCF/RAD21, FOXA1_dTAG_0h
- GSM8877803 22Rv1 cells, Input_CTCF/RAD21, FOXA1_dTAG_24h
- GSM8877804 LNCap cells, FOXA1, Ctrl (ChIP)
- GSM8877805 LNCap cells, FOXA1, FOXA1 knockdown (ChIP)
- GSM8877806 LNCap cells, NIPBL, Ctrl (ChIP)
- GSM8877807 LNCap cells, NIPBL, FOXA1 knockdown (ChIP)
- GSM8877808 LNCap cells, Input_Ctrl
- GSM8877809 LNCap cells, Input_FOXA1 knockdown
- GSM8877810 A549 cells, NIPBL, Ctrl (ChIP)
- GSM8877811 A549 cells, NIPBL, Ctrl (Input)
- GSM8877812 A549 cells, NIPBL, FOXA1 knockdown (ChIP)
- GSM8877813 A549 cells, NIPBL, FOXA1 knockdown (Input)
- GSM8877814 A549 cells, NIPBL, ETS1 knockdown (ChIP)
- GSM8877815 A549 cells, NIPBL, ETS1 knockdown (Input)
- GSM8877816 22Rv1 cells, FOXA1, WT (ChIP)
- GSM8877817 22Rv1 cells, FOXA1, R219S mutation (ChIP)
- GSM8877818 22Rv1 cells, NIPBL, WT (ChIP)
- GSM8877819 22Rv1 cells, NIPBL, R219S mutation (ChIP)
- GSM8877820 22Rv1 cells, WT (Input)
- GSM8877821 22Rv1 cells, R219S mutation (Input)
- GSM8877822 mouse liver tissue, FOXA1, rep1 (ChIP)
- GSM8877823 mouse liver tissue, FOXA1, rep2 (ChIP)
- GSM8877824 mouse liver tissue, NIPBL, rep1 (ChIP)
- GSM8877825 mouse liver tissue, NIPBL, rep2 (ChIP)
+ 28 more — browse all 68 samples with per-sample file links →
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