NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions.
A unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and transcriptionally repressed heterochromatin. In metazoa, lamin proteins preserve nuclear integrity and higher order heterochromatin organization at the nuclear periphery, but no...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3313915?pdf=render |
| _version_ | 1818570090795237376 |
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| author | Kelly N DuBois Sam Alsford Jennifer M Holden Johanna Buisson Michal Swiderski Jean-Mathieu Bart Alexander V Ratushny Yakun Wan Philippe Bastin J David Barry Miguel Navarro David Horn John D Aitchison Michael P Rout Mark C Field |
| author_facet | Kelly N DuBois Sam Alsford Jennifer M Holden Johanna Buisson Michal Swiderski Jean-Mathieu Bart Alexander V Ratushny Yakun Wan Philippe Bastin J David Barry Miguel Navarro David Horn John D Aitchison Michael P Rout Mark C Field |
| author_sort | Kelly N DuBois |
| collection | DOAJ |
| description | A unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and transcriptionally repressed heterochromatin. In metazoa, lamin proteins preserve nuclear integrity and higher order heterochromatin organization at the nuclear periphery, but no non-metazoan lamin orthologues have been identified, despite the likely presence of nucleoskeletal elements in many lineages. This suggests a metazoan-specific origin for lamins, and therefore that distinct protein elements must compose the nucleoskeleton in other lineages. The trypanosomatids are highly divergent organisms and possess well-documented but remarkably distinct mechanisms for control of gene expression, including polycistronic transcription and trans-splicing. NUP-1 is a large protein localizing to the nuclear periphery of Trypanosoma brucei and a candidate nucleoskeletal component. We sought to determine if NUP-1 mediates heterochromatin organization and gene regulation at the nuclear periphery by examining the influence of NUP-1 knockdown on morphology, chromatin positioning, and transcription. We demonstrate that NUP-1 is essential and part of a stable network at the inner face of the trypanosome nuclear envelope, since knockdown cells have abnormally shaped nuclei with compromised structural integrity. NUP-1 knockdown also disrupts organization of nuclear pore complexes and chromosomes. Most significantly, we find that NUP-1 is required to maintain the silenced state of developmentally regulated genes at the nuclear periphery; NUP-1 knockdown results in highly specific mis-regulation of telomere-proximal silenced variant surface glycoprotein (VSG) expression sites and procyclin loci, indicating a disruption to normal chromatin organization essential to life-cycle progression. Further, NUP-1 depletion leads to increased VSG switching and therefore appears to have a role in control of antigenic variation. Thus, analogous to vertebrate lamins, NUP-1 is a major component of the nucleoskeleton with key roles in organization of the nuclear periphery, heterochromatin, and epigenetic control of developmentally regulated loci. |
| first_indexed | 2024-12-14T06:56:18Z |
| format | Article |
| id | doaj.art-540a2f56b632434b9fa88c329396740d |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-14T06:56:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Biology |
| spelling | doaj.art-540a2f56b632434b9fa88c329396740d2022-12-21T23:12:39ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852012-01-01103e100128710.1371/journal.pbio.1001287NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions.Kelly N DuBoisSam AlsfordJennifer M HoldenJohanna BuissonMichal SwiderskiJean-Mathieu BartAlexander V RatushnyYakun WanPhilippe BastinJ David BarryMiguel NavarroDavid HornJohn D AitchisonMichael P RoutMark C FieldA unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and transcriptionally repressed heterochromatin. In metazoa, lamin proteins preserve nuclear integrity and higher order heterochromatin organization at the nuclear periphery, but no non-metazoan lamin orthologues have been identified, despite the likely presence of nucleoskeletal elements in many lineages. This suggests a metazoan-specific origin for lamins, and therefore that distinct protein elements must compose the nucleoskeleton in other lineages. The trypanosomatids are highly divergent organisms and possess well-documented but remarkably distinct mechanisms for control of gene expression, including polycistronic transcription and trans-splicing. NUP-1 is a large protein localizing to the nuclear periphery of Trypanosoma brucei and a candidate nucleoskeletal component. We sought to determine if NUP-1 mediates heterochromatin organization and gene regulation at the nuclear periphery by examining the influence of NUP-1 knockdown on morphology, chromatin positioning, and transcription. We demonstrate that NUP-1 is essential and part of a stable network at the inner face of the trypanosome nuclear envelope, since knockdown cells have abnormally shaped nuclei with compromised structural integrity. NUP-1 knockdown also disrupts organization of nuclear pore complexes and chromosomes. Most significantly, we find that NUP-1 is required to maintain the silenced state of developmentally regulated genes at the nuclear periphery; NUP-1 knockdown results in highly specific mis-regulation of telomere-proximal silenced variant surface glycoprotein (VSG) expression sites and procyclin loci, indicating a disruption to normal chromatin organization essential to life-cycle progression. Further, NUP-1 depletion leads to increased VSG switching and therefore appears to have a role in control of antigenic variation. Thus, analogous to vertebrate lamins, NUP-1 is a major component of the nucleoskeleton with key roles in organization of the nuclear periphery, heterochromatin, and epigenetic control of developmentally regulated loci.http://europepmc.org/articles/PMC3313915?pdf=render |
| spellingShingle | Kelly N DuBois Sam Alsford Jennifer M Holden Johanna Buisson Michal Swiderski Jean-Mathieu Bart Alexander V Ratushny Yakun Wan Philippe Bastin J David Barry Miguel Navarro David Horn John D Aitchison Michael P Rout Mark C Field NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biology |
| title | NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. |
| title_full | NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. |
| title_fullStr | NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. |
| title_full_unstemmed | NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. |
| title_short | NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. |
| title_sort | nup 1 is a large coiled coil nucleoskeletal protein in trypanosomes with lamin like functions |
| url | http://europepmc.org/articles/PMC3313915?pdf=render |
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