| First Author | Kiefer L | Year | 2024 |
| Journal | Science | Volume | 385 |
| Issue | 6707 | Pages | eadm9802 |
| PubMed ID | 39052779 | Mgi Jnum | J:362865 |
| Mgi Id | MGI:7705400 | Doi | 10.1126/science.adm9802 |
| Citation | Kiefer L, et al. (2024) Tuning cohesin trajectories enables differential readout of the Pcdhalpha cluster across neurons. Science 385(6707):eadm9802 |
| abstractText | Expression of Protocadherin (Pcdh) genes is critical to the generation of neuron identity and wiring of the nervous system. Pcdhalpha genes are arranged in clusters and exhibit a range of expression profiles, from stochastic to deterministic. Because Pcdhalpha promoters have high sequence identity and share distal enhancers, how distinct neurons choose which gene to express remains unclear. We show that the interplay between multiple enhancers, epigenetics, and genome folding orchestrates differential readouts of the locus across neurons. The probability of Pcdhalpha promoter choice depends on enhancer/promoter encounters catalyzed by cohesin, whose extrusion trajectories determine the likelihood that an individual promoter can "escape" heterochromatin-mediated silencing. We propose that tunable locus-specific regulatory elements and cell type-specific cohesin activity underlie the generation of cellular diversity by Pcdh genes. |
