GEO series

NELF prevents transcriptional readthrough into DNA replication zones in cancer cells

GSE253121 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 70 samples Submitted 2025/12/13 Platform GPL24676

Summary

Regulation of RNA polymerase II (Pol II) transcription is closely associated with cell proliferation. However, it remains unclear how the Pol II transcription program is rewired in cancer to promote uncontrolled growth. Here, we find that expression of NELFCD, a known negative transcription elongation factor, is upregulated in colorectal tumors. Auxin-dependent protein degradation of NELF-C in combination with nascent transcript sequencing demonstrates a direct role of NELF-C on Pol II transcription in this cancer. Strikingly, we demonstrate that the acute loss of NELF-C protein globally redistributes termination factors and perturbs Pol II transcription termination. These changes drive pervasive Pol II transcription into DNA replication zones, leading to transcription-replication conflict that may block the cell cycle in G1 or early S phase. Our findings reveal a previously unrecognized role of NELF in transcription termination and highlight NELF as a potential therapeutic target in colorectal cancer.

Published in

Nakayama C, Fang Q, Daigaku Y et al. · EMBO reports 2026 · PMID 41721097 · doi:10.1038/s44319-026-00700-z

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Direct links to NCBI, no account and no request form: the whole study as GSE253121_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 70 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1064075 and SRA study SRP485475. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41721097) ↗

Study design

20 conditions, mostly in duplicate

ATAC_0h ×2 ATAC_4h ×2 ATAC_24h ×2 RNAseq_pA_0h ×2 RNAseq_pA_4h ×2 RNAseq_Nuclear_pA_0h ×2 RNAseq_Nuclear_pA_4h ×2 RNAseq_Nuclear_pA_12h ×2 +12 more

Supports a between-group comparison across 40 samples.

20 replicated groups read from the first 40 of 70 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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