Yu, Ruofan, Roseman, Shelby, Siegenfeld, Allison P, Gardner, Zachary, Nguyen, Son C, Tran, Khoa A, Joyce, Eric F, Jain, Rajan, Liau, Brian B, Krantz, Ian D, Alexander, Katherine A, Berger, Shelley L (February 2025) CTCF/RAD21 organize the ground state of chromatin-nuclear speckle association. Nature Structural & Molecular Biology. ISSN 1545-9993 (Public Dataset)
Abstract
Recent findings indicate that nuclear speckles, a distinct type of nuclear body, interact with certain chromatin regions in a ground state. Here, we report that the chromatin structural factors CTCF and cohesin are required for full ground-state association between DNA and nuclear speckles. We identified a putative speckle-targeting motif (STM) within cohesin subunit RAD21 and demonstrated that the STM is required for chromatin-nuclear speckle association, disruption of which also impaired induction of speckle-associated genes. Depletion of the cohesin-releasing factor WAPL, which stabilizes cohesin on chromatin, resulted in reinforcement of DNA-speckle contacts and enhanced inducibility of speckle-associated genes. Additionally, we observed disruption of chromatin-nuclear speckle association in patient-derived cells with Cornelia de Lange syndrome, a congenital neurodevelopmental disorder involving defective cohesin pathways. In summary, our findings reveal a mechanism for establishing the ground state of chromatin-speckle association and promoting gene inducibility, with relevance to human disease.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > nuclear speckles |
| CSHL Authors: | |
| Communities: | CSHL labs > Alexander lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 21 February 2025 |
| Date Deposited: | 24 Feb 2025 13:03 |
| Last Modified: | 24 Feb 2025 13:03 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/41800 |
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