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The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A
Centromere identity and its epigenetic maintenance require the incorporation of a histone H3 variant called CENP-A at centromeres. CENP-A mislocalization to ectopic sites may disrupt chromatin-based processes and chromosome segregation, so it is important to uncover the mechanisms by which this vari...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197964/ https://www.ncbi.nlm.nih.gov/pubmed/25128498 http://dx.doi.org/10.1101/gad.243113.114 |
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author | Deyter, Gary M.R. Biggins, Sue |
author_facet | Deyter, Gary M.R. Biggins, Sue |
author_sort | Deyter, Gary M.R. |
collection | PubMed |
description | Centromere identity and its epigenetic maintenance require the incorporation of a histone H3 variant called CENP-A at centromeres. CENP-A mislocalization to ectopic sites may disrupt chromatin-based processes and chromosome segregation, so it is important to uncover the mechanisms by which this variant is exclusively localized to centromeres. Here, we identify a role for the conserved chromatin-modifying complex FACT (facilitates chromatin transcription/transactions) in preventing budding yeast CENP-A(Cse4) mislocalization to euchromatin by mediating its proteolysis. The Spt16 subunit of the FACT complex binds to Psh1 (Pob3/Spt16/histone), an E3 ubiquitin ligase that targets CENP-A(Cse4) for degradation. The interaction between Psh1 and Spt16 is critical for both CENP-A(Cse4) ubiquitylation and its exclusion from euchromatin. We found that Psh1 cannot efficiently ubiquitylate CENP-A(Cse4) nucleosomes in vitro, suggesting that additional factors must facilitate CENP-A(Cse4) removal from chromatin in vivo. Consistent with this, a Psh1 mutant that cannot associate with FACT has a reduced interaction with CENP-A(Cse4) in vivo. Together, our data identify a previously unknown mechanism to maintain centromere identity and genomic stability through the FACT-mediated degradation of ectopically localized CENP-A(Cse4). |
format | Online Article Text |
id | pubmed-4197964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41979642015-02-15 The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A Deyter, Gary M.R. Biggins, Sue Genes Dev Research Paper Centromere identity and its epigenetic maintenance require the incorporation of a histone H3 variant called CENP-A at centromeres. CENP-A mislocalization to ectopic sites may disrupt chromatin-based processes and chromosome segregation, so it is important to uncover the mechanisms by which this variant is exclusively localized to centromeres. Here, we identify a role for the conserved chromatin-modifying complex FACT (facilitates chromatin transcription/transactions) in preventing budding yeast CENP-A(Cse4) mislocalization to euchromatin by mediating its proteolysis. The Spt16 subunit of the FACT complex binds to Psh1 (Pob3/Spt16/histone), an E3 ubiquitin ligase that targets CENP-A(Cse4) for degradation. The interaction between Psh1 and Spt16 is critical for both CENP-A(Cse4) ubiquitylation and its exclusion from euchromatin. We found that Psh1 cannot efficiently ubiquitylate CENP-A(Cse4) nucleosomes in vitro, suggesting that additional factors must facilitate CENP-A(Cse4) removal from chromatin in vivo. Consistent with this, a Psh1 mutant that cannot associate with FACT has a reduced interaction with CENP-A(Cse4) in vivo. Together, our data identify a previously unknown mechanism to maintain centromere identity and genomic stability through the FACT-mediated degradation of ectopically localized CENP-A(Cse4). Cold Spring Harbor Laboratory Press 2014-08-15 /pmc/articles/PMC4197964/ /pubmed/25128498 http://dx.doi.org/10.1101/gad.243113.114 Text en © 2014 Deyter and Biggins; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Deyter, Gary M.R. Biggins, Sue The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title | The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title_full | The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title_fullStr | The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title_full_unstemmed | The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title_short | The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A |
title_sort | fact complex interacts with the e3 ubiquitin ligase psh1 to prevent ectopic localization of cenp-a |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197964/ https://www.ncbi.nlm.nih.gov/pubmed/25128498 http://dx.doi.org/10.1101/gad.243113.114 |
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