RT Journal Article
SR Electronic
T1 Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 287532
DO 10.1101/287532
A1 A. Horta
A1 K. Monahan
A1 E. Bashkirova
A1 S. Lomvardas
YR 2018
UL http://biorxiv.org/content/early/2018/03/23/287532.abstract
AB The eukaryotic genome is partitioned into topologically associated domains (TADs) that assemble into compartments of shared chromatin valance. This architecture is influenced by the physical constraints imposed by the DNA polymer, which restricts DNA interactions predominantly to genomic segments from the same chromosome. Here, we report a dramatic divergence from this pattern of nuclear organization that occurs during the differentiation and specification of mouse olfactory sensory neurons (OSNs). In situ HiC on FAC-sorted OSNs shows that olfactory receptor (OR) genes from numerous chromosomes make frequent, extensive, and highly specific interchromosomal contacts that strengthen with differentiation. Moreover, in terminally differentiated OSNs, >30 intergenic enhancers generate a multi-chromosomal hub that associates only with the single active OR from a pool of ∼1400 genes. Our data reveal that interchromosomal interactions can form with remarkable stereotypy between like neurons, generating a regulatory landscape for stochastic, monogenic, and monoallelic gene expression.