Authors
Ziyu Zhao, Omar A Payán Parra, Shin-Ichiro Fujita, Francesco Musella, Nicolas J Scrutton Alvarado, Frank Alber, Yue Yang, Tomoko Yamada
Published in
Nature cell biology. Aug 10, 2026. Epub Aug 10, 2026.
Abstract
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 signalling proteins. Genomic regions within this subcompartment are enriched in the outer half of the nucleus, whereas 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.
PMID:
42575995
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.
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