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DGCR8 promotes RNA polymerase II pause release independently of DROSHA [ChIP-seq]

GSE324933 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 32 samples Submitted 2026/07/30 Platform GPL24247
Summary
DiGeorge syndrome critical region gene 8 (DGCR8) is best known as the RNA binding subunit of the microprocessor complex required for canonical microRNA (miRNA) biogenesis. Whether DGCR8 also exerts a direct, microprocessor independent function in the RNA polymerase II (Pol II) transcription cycle remains unclear. Here, we combined rapid, acute protein depletion with nascent transcription profiling and uncovered a non-canonical role for DGCR8 in transcriptional control in mouse embryonic stem cells (mESCs). We found that DGCR8 broadly occupies promoters and transcription start sites (TSSs) with limited co occupancy by its catalytic microprocessor partner DROSHA. Acute DGCR8 depletion triggers an immediate, genome wide reduction in nascent RNA synthesis that is not phenocopied by acute DROSHA depletion. Mechanistically, DGCR8 loss decreases Pol II engagement at promoters and induces a pervasive blockade in promoter proximal pause release, indicating a direct requirement for DGCR8 in the transition to productive elongation. We further identified physical interactions linking DGCR8 to Enhancer of Rudimentary Homolog (ERH) and the elongation factor SPT5, and showed that acute ERH depletion similarly suppresses nascent transcription. Together, our data implicate a potential model in which promoter bound DGCR8 facilitates Pol II pause release through an ERH–SPT5 linked regulatory network, establishing DGCR8 as a non canonical regulator of the core transcription machinery.
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Direct links to NCBI, no account and no request form: the whole study as GSE324933_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 32 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1438123 and SRA study SRP684071. Searching any of these in the dataset finder brings you back here.

Study design
14 conditions, mostly in duplicate
mES, dTAG_DGCR8, DMSO, FLAG, ×2 mES, dTAG_DGCR8, dTAG24h, FLAG, ×2 mES, dTAG_DROSHA, DMSO, FLAG, ×2 mES, dTAG_DROSHA, dTAG24h, FLAG, ×2 mES, dTAG_ERH, non_dTAG, SPT5, ×2 mES, dTAG_ERH, dTAG_3h, SPT5, ×2 mES, dTAG_DROSHA, non_dTAG, ERH, ×2 mES, dTAG_DROSHA, non_dTAG, SPT5, ×2 +10 more

Supports a between-group comparison across 28 samples.

14 replicated groups read from 32 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.

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