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Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site

Promyelocytic leukemia nuclear bodies (PML-NBs)/nuclear domain 10s (ND10s) are nuclear structures that contain many transcriptional and chromatin regulatory factors. One of these, Sp100, is expressed from a single-copy gene and spliced into four isoforms (A, B, C, and HMG), which differentially regu...

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Autores principales: Newhart, Alyshia, Negorev, Dmitri G., Rafalska-Metcalf, Ilona U., Yang, Tian, Maul, Gerd G., Janicki, Susan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639056/
https://www.ncbi.nlm.nih.gov/pubmed/23485562
http://dx.doi.org/10.1091/mbc.E12-09-0669
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author Newhart, Alyshia
Negorev, Dmitri G.
Rafalska-Metcalf, Ilona U.
Yang, Tian
Maul, Gerd G.
Janicki, Susan M.
author_facet Newhart, Alyshia
Negorev, Dmitri G.
Rafalska-Metcalf, Ilona U.
Yang, Tian
Maul, Gerd G.
Janicki, Susan M.
author_sort Newhart, Alyshia
collection PubMed
description Promyelocytic leukemia nuclear bodies (PML-NBs)/nuclear domain 10s (ND10s) are nuclear structures that contain many transcriptional and chromatin regulatory factors. One of these, Sp100, is expressed from a single-copy gene and spliced into four isoforms (A, B, C, and HMG), which differentially regulate transcription. Here we evaluate Sp100 function in single cells using an inducible cytomegalovirus-promoter–regulated transgene, visualized as a chromatinized transcription site. Sp100A is the isoform most strongly recruited to the transgene array, and it significantly increases chromatin decondensation. However, Sp100A cannot overcome Daxx- and α-thalassemia mental retardation, X-linked (ATRX)–mediated transcriptional repression, which indicates that PML-NB/ND10 factors function within a regulatory hierarchy. Sp100A increases and Sp100B, which contains a SAND domain, decreases acetyl-lysine regulatory factor levels at activated sites, suggesting that Sp100 isoforms differentially regulate transcription by modulating lysine acetylation. In contrast to Daxx, ATRX, and PML, Sp100 is recruited to activated arrays in cells expressing the herpes simplex virus type 1 E3 ubiquitin ligase, ICP0, which degrades all Sp100 isoforms except unsumoylated Sp100A. The recruitment Sp100A(K297R), which cannot be sumoylated, further suggests that sumoylation plays an important role in regulating Sp100 isoform levels at transcription sites. This study provides insight into the ways in which viruses may modulate Sp100 to promote their replication cycles.
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spelling pubmed-36390562013-07-16 Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site Newhart, Alyshia Negorev, Dmitri G. Rafalska-Metcalf, Ilona U. Yang, Tian Maul, Gerd G. Janicki, Susan M. Mol Biol Cell Articles Promyelocytic leukemia nuclear bodies (PML-NBs)/nuclear domain 10s (ND10s) are nuclear structures that contain many transcriptional and chromatin regulatory factors. One of these, Sp100, is expressed from a single-copy gene and spliced into four isoforms (A, B, C, and HMG), which differentially regulate transcription. Here we evaluate Sp100 function in single cells using an inducible cytomegalovirus-promoter–regulated transgene, visualized as a chromatinized transcription site. Sp100A is the isoform most strongly recruited to the transgene array, and it significantly increases chromatin decondensation. However, Sp100A cannot overcome Daxx- and α-thalassemia mental retardation, X-linked (ATRX)–mediated transcriptional repression, which indicates that PML-NB/ND10 factors function within a regulatory hierarchy. Sp100A increases and Sp100B, which contains a SAND domain, decreases acetyl-lysine regulatory factor levels at activated sites, suggesting that Sp100 isoforms differentially regulate transcription by modulating lysine acetylation. In contrast to Daxx, ATRX, and PML, Sp100 is recruited to activated arrays in cells expressing the herpes simplex virus type 1 E3 ubiquitin ligase, ICP0, which degrades all Sp100 isoforms except unsumoylated Sp100A. The recruitment Sp100A(K297R), which cannot be sumoylated, further suggests that sumoylation plays an important role in regulating Sp100 isoform levels at transcription sites. This study provides insight into the ways in which viruses may modulate Sp100 to promote their replication cycles. The American Society for Cell Biology 2013-05-01 /pmc/articles/PMC3639056/ /pubmed/23485562 http://dx.doi.org/10.1091/mbc.E12-09-0669 Text en © 2013 Newhart et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Newhart, Alyshia
Negorev, Dmitri G.
Rafalska-Metcalf, Ilona U.
Yang, Tian
Maul, Gerd G.
Janicki, Susan M.
Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title_full Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title_fullStr Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title_full_unstemmed Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title_short Sp100A promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
title_sort sp100a promotes chromatin decondensation at a cytomegalovirus-promoter–regulated transcription site
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639056/
https://www.ncbi.nlm.nih.gov/pubmed/23485562
http://dx.doi.org/10.1091/mbc.E12-09-0669
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