| Autor: |
Kania EE, Fenix A, Marciniak DM, Lin Q, Bianchi S, Hristov B, Li S, Camplisson CK, Fields R, Beliveau BJ, Schweppe DK, Noble WS, Ong SE, Bertero A, Murry CE, Shechner DM |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 13. Date of Electronic Publication: 2024 Nov 13. |
| DOI: |
10.1101/2024.11.05.622011 |
| Abstrakt: |
Eukaryotic nuclei adopt a highly compartmentalized architecture that influences nearly all genomic processes. Understanding how this architecture impacts gene expression has been hindered by a lack of tools for elucidating the molecular interactions at individual genomic loci. Here, we adapt oligonucleotide-mediated proximity-interactome mapping (O-MAP) to biochemically characterize discrete, micron-scale nuclear neighborhoods. By targeting O-MAP to introns within the TTN pre-mRNA, we systematically map the chromatin loci, RNAs, and proteins within a muscle-specific RNA factory organized around the TTN locus. This reveals an unanticipated compartmental architecture that organizes cis - and trans -interacting chromosomal domains, including a hub of transcriptionally silenced chromatin. The factory also recruits dozens of unique RNA-binding and chromatin-scaffolding factors, including QKI and SAFB, along with their target transcripts. Loss of the cardiac-specific splicing factor RBM20-a master regulator of TTN splicing that is mutated in dilated cardiomyopathy-remodels nearly every facet of this architecture. This establishes O-MAP as a pioneering method for probing single-locus, microcompartment-level interactions that are opaque to conventional tools. Our findings suggest new mechanisms by which coding genes can "moonlight" in nuclear-architectural roles. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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