| Title: |
The PRR14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting |
| Authors: |
Dunlevy, Kelly L.; Medvedeva, Valentina; Wilson, Jade E.; Hoque, Mohammed; Pellegrin, Trinity; Maynard, Adam; Kremp, Madison M.; Wasserman, Jason S.; Poleshko, Andrey; Katz, Richard A. |
| Publisher Information: |
The Company of Biologists Ltd |
| Publication Year: |
2020 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
RESEARCH ARTICLE |
| Description: |
A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via ‘tethering proteins’ that function to bridge heterochromatin and the nuclear membrane or nuclear lamina. We previously identified a human tethering protein, PRR14, that binds heterochromatin through an N-terminal domain, but the mechanism and regulation of nuclear lamina association remained to be investigated. Here we identify an evolutionarily conserved PRR14 nuclear lamina binding domain (LBD) that is both necessary and sufficient for positioning of PRR14 at the nuclear lamina. We show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation and dephosphorylation of the LBD. Furthermore, we identify a PP2A phosphatase recognition motif within the evolutionarily conserved C-terminal Tantalus domain of PRR14. Disruption of this motif affects PRR14 localization to the nuclear lamina. The overall findings demonstrate a heterochromatin anchoring mechanism whereby the PRR14 tether simultaneously binds heterochromatin and the nuclear lamina through two separable modular domains. Our findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://jcs.biologists.org/cgi/content/short/133/10/jcs240416; http://dx.doi.org/10.1242/jcs.240416 |
| DOI: |
10.1242/jcs.240416 |
| Availability: |
http://jcs.biologists.org/cgi/content/short/133/10/jcs240416; https://doi.org/10.1242/jcs.240416 |
| Rights: |
Copyright (C) 2020, Company of Biologists |
| Accession Number: |
edsbas.33738C8C |
| Database: |
BASE |