RT Journal Article
SR Electronic
T1 Mega-Enhancer Bodies Organize Neuronal Long Genes in the Cerebellum
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.07.19.549737
DO 10.1101/2023.07.19.549737
A1 Zhao, Ziyu
A1 Parra, Omar Payán
A1 Musella, Francesco
A1 Scrutton-Alvarado, Nicolas
A1 Fujita, Shin-ichiro
A1 Alber, Frank
A1 Yang, Yue
A1 Yamada, Tomoko
YR 2023
UL http://biorxiv.org/content/early/2023/07/25/2023.07.19.549737.abstract
AB Dynamic regulation of gene expression plays a key role in establishing the diverse neuronal cell types in the brain. Recent findings in genome biology suggest that three-dimensional (3D) genome organization has important, but mechanistically poorly understood functions in gene transcription. Beyond local genomic interactions between promoters and enhancers, we find that cerebellar granule neurons undergoing differentiation in vivo exhibit striking increases in long-distance genomic interactions between transcriptionally active genomic loci, which are separated by tens of megabases within a chromosome or located on different chromosomes. Among these interactions, we identify a nuclear subcompartment enriched for near-megabase long enhancers and their associated neuronal long genes encoding synaptic or signaling proteins. Neuronal long genes are differentially recruited to this enhancer-dense subcompartment to help shape the transcriptional identities of granule neuron subtypes in the cerebellum. SPRITE analyses of higher-order genomic interactions, together with IGM-based 3D genome modeling and imaging approaches, reveal that the enhancer-dense subcompartment forms prominent nuclear structures, which we term mega-enhancer bodies. These novel nuclear bodies reside in the nuclear periphery, away from other transcriptionally active structures, including nuclear speckles located in the nuclear interior. Together, our findings define additional layers of higher-order 3D genome organization closely linked to neuronal maturation and identity in the brain.Competing Interest StatementThe authors have declared no competing interest.