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Dunlevy KL , Medvedeva V , Wilson JE , Hoque M , Pellegrin T , Maynard A , Kremp MM , Wasserman JS , Poleshko A , Katz RA
The PRR14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting
J Cell Sci. 2020 May;133(10)
PMID: 32317397 PMCID: PMC7272351 URL: https://www.ncbi.nlm.nih.gov/pubmed/32317397
AbstractA 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 identified previously 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 also show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation-dephosphorylation of the LBD. Furthermore, we identified a PP2A phosphatase recognition motif within the evolutionarily conserved PRR14 C-terminal Tantalus domain. Disruption of this motif affected 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. The findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina.
Notes1477-9137 Dunlevy, Kelly L ORCID: http://orcid.org/0000-0001-7310-1011 Medvedeva, Valentina Wilson, Jade E Hoque, Mohammed Pellegrin, Trinity Maynard, Adam Kremp, Madison M Wasserman, Jason S Poleshko, Andrey ORCID: http://orcid.org/0000-0002-6656-2941 Katz, Richard A ORCID: http://orcid.org/0000-0002-9026-002X Journal Article England J Cell Sci. 2020 May 27;133(10). pii: jcs.240416. doi: 10.1242/jcs.240416.