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Publication : Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding.

First Author  Kadota S Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  2606
PubMed ID  32451376 Mgi Jnum  J:292071
Mgi Id  MGI:6447129 Doi  10.1038/s41467-020-16394-3
Citation  Kadota S, et al. (2020) Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding. Nat Commun 11(1):2606
abstractText  Nucleoporin proteins (Nups) have been proposed to mediate spatial and temporal chromatin organization during gene regulation. Nevertheless, the molecular mechanisms in mammalian cells are not well understood. Here, we report that Nucleoporin 153 (NUP153) interacts with the chromatin architectural proteins, CTCF and cohesin, and mediates their binding across cis-regulatory elements and TAD boundaries in mouse embryonic stem (ES) cells. NUP153 depletion results in altered CTCF and cohesin binding and differential gene expression - specifically at the bivalent developmental genes. To investigate the molecular mechanism, we utilize epidermal growth factor (EGF)-inducible immediate early genes (IEGs). We find that NUP153 controls CTCF and cohesin binding at the cis-regulatory elements and POL II pausing during the basal state. Furthermore, efficient IEG transcription relies on NUP153. We propose that NUP153 links the nuclear pore complex (NPC) to chromatin architecture allowing genes that are poised to respond rapidly to developmental cues to be properly modulated.
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