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Mega-Enhancers Compartmentalize Transcriptionally Active Long Genes in the Brain [ChIP-Seq]

GSE339012 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 22 samples Submitted 2026/07/21 Platform GPL21626
Summary
Exceptionally long genes and cis-regulatory enhancers are selectively activated in mammalian brain neurons, and these loci are mutation hotspots in neurological disorders. However, the organization of these large genomic elements at the level of chromosome folding, beyond local enhancer-promoter interactions, remains poorly understood. Here, we report the discovery of a genomic subcompartment in the mouse cerebellum formed by near-megabase long enhancers and their associated long genes encoding synaptic or signaling proteins. Genomic regions within this subcompartment are enriched in the outer-half of the nucleus, while other transcriptionally active structures are enriched in the nuclear interior. Using an in vivo CRISPR genetic mini-screen, we uncover a specific role for the transcription factor Etv1 in coupling the compartmentalization of neuronal long genes with their expression. Together, our study defines mechanisms that organize transcriptionally active genes across chromosomes in the mammalian brain.
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Direct links to NCBI, no account and no request form: the whole study as GSE339012_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 22 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1496804 and SRA study SRP718882. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly in triplicate
Brd4 ChIP-seq cerebellum, ×4 H3K27ac ChIP-seq GN, ctrl, FANS, IVE+day8, ×3 H3K27ac ChIP-seq GN, ctrl, FANS, IVE+day14, ×3 H3K27ac ChIP-seq GN, etv1 KD, FANS, IVE+day8, ×3 H3K27ac ChIP-seq GN, ubash3b eKD, FANS, IVE+d… ×3 H3K27ac ChIP-seq GN, ctrl, FANS, IVE+day4, ×2 H3K27ac ChIP-seq GN, brd4 KD, FANS, IVE+day8, ×2 H3K27ac ChIP-seq GN, slc8a1 eKD, FANS, IVE+da… ×2

Supports a between-group comparison across 22 samples.

8 replicated groups read from 22 sample titles; they account for 22 of them. Check it against the sample list below before relying on it.

Samples in this study
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