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

Newhart, Alyshia; Negorev, Dmitri; Rafalska-Metcalf, Ilona U.; Yang, Tian; Maul, Gerd G.; Janicki, Susan M.

doi:10.1091/mbc.e12-09-0669

Cited by 22 publications

(22 citation statements)

References 53 publications

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“…To generate a stable cell line expressing human IRF7, a lentiviral vector previously described was used (20). Plasmids encoding for EYFP fused human SP100B and SP100C were a kind gift from Dr. Susan M. Janicki (Wistar Institute, Philadelphia, PA) and were previously described (54).…”

Section: Methodsmentioning

confidence: 99%

Mitogen-activated Protein Kinase-mediated Licensing of Interferon Regulatory Factor 3/7 Reinforces the Cell Response to Virus

Schmid¹,

Sachs²,

tenOever³

2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Mitogen-activated Protein Kinase-mediated Licensing of Interferon Regulatory Factor 3/7 Reinforces the Cell Response to Virus

Schmid¹,

Sachs²,

tenOever³

2014

Journal of Biological Chemistry

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“…All of these domains have previously been shown to mediate association with chromatin (3,(16)(17)(18)(19). Recently, Newhart and coworkers proposed the model that Sp100A increases chromatin decondensation, whereas the SAND domain in isoforms Sp100B, -C, and -HMG promotes chromatin condensation, suggesting that these proteins play a different role in transcriptional regulation (20).…”

Section: Importancementioning

confidence: 99%

“…Recently, Newhart et al reported that Sp100A promotes chromatin decondensation at cytomegalovirus (CMV) promoter-regulated transcription sites. In contrast, Sp100B, containing an additional SAND domain, promotes chromatin condensation, and thus transcriptional repression (20). To test whether Sp100 also affects transcription from Ad promoters, we investigated Ad E1A, E2early, pIX, and E3 promoter activity in the presence of either Sp100A or Sp100B, as stable knockdown of each isoform was not feasible due to sequence similarity (Fig.…”

Section: Sp100 Depletion Promotes Ad Progeny Production and Early Virmentioning

confidence: 99%

Sp100 Isoform-Specific Regulation of Human Adenovirus 5 Gene Expression

Berscheminski

Wimmer

Brun

et al. 2014

J Virol

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Promyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating capabilities of Sp100A and simultaneously limit repression by Sp100B, -C, and -HMG, adenoviruses (Ads) employ several features to selectively and individually target these isoforms. Ads induce relocalization of Sp100B, -C, and -HMG from PML-NBs prior to association with viral replication centers. In contrast, Sp100A is kept at the PML tracks that surround the newly formed viral replication centers as designated sites of active transcription. We concluded that the host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression. Ad-dependent loss of Sp100 SUMOylation is another crucial part of the virus repertoire to counteract intrinsic immunity by circumventing Sp100 association with HP1, therefore limiting chromatin condensation. We provide evidence that Ad selectively counteracts antiviral responses and, at the same time, benefits from PML-NB-associated components which support viral gene expression by actively recruiting them to PML track-like structures. Our findings provide insights into novel strategies for manipulating transcriptional regulation to either inactivate or amplify viral gene expression. IMPORTANCEWe describe an adenoviral evasion strategy that involves isoform-specific and active manipulation of the PML-associated restriction factor Sp100. Recently, we reported that the adenoviral transactivator E1A targets PML-II to efficiently activate viral transcription. In contrast, the PML-associated proteins Daxx and ATRX are inhibited by early viral factors. We show that this concept is more intricate and significant than originally believed, since adenoviruses apparently take advantage of specific PML-NBassociated proteins and simultaneously inhibit antiviral measures to maintain the viral infectious program. Specifically, we observed Ad-induced relocalization of the Sp100 isoforms B, C, and HMG from PML-NBs juxtaposed with viral replication centers. In contrast, Sp100A is retained at Ad-induced PML tracks that surround the newly formed viral replication centers, acting as designated sites of active transcription. The host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression.

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“…For example, strand-specific quantitative RT-PCR, high-throughput sequencing, and RNA FISH have been used to analyze RNA expression (Newhart et al , 2013b). Chromatin immunoprecipitation has been used to monitor factor recruitment and histone post-translational modifications (PTMs) as well as to identify sequence specific enrichment (Newhart et al, 2013a; Newhart et al, 2012; Shanbhag et al, 2010; Tang et al, 2013; Zhao et al, 2011). Validated hypotheses about gene regulatory mechanisms can be tested at endogenous genes.…”

Section: Presentationmentioning

confidence: 99%

Seeing Is Believing: Visualizing Transcriptional Dynamics in Single Cells

Newhart

Janicki

2013

Journal Cellular Physiology

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For a gene to be expressed, the functions of multiple molecular machines must be coordinated at the site of transcription. To understand the role of nuclear organization in transcription, it is necessary to visualize the dynamic interactions of regulatory factors with chromatin and RNA. It is currently possible to localize individual transcription sites in single living mammalian cells by engineering reporter gene constructs to include sequence elements which permit the visualization of nucleic acids in vivo. Upon stable integration, these transgenes form chromatinized arrays, which can be imaged during activation to obtain high-resolution quantitative information about transcriptional dynamics. Modeling can suggest new hypotheses about gene regulation, which can be tested both in the single-cell imaging system and at endogenous genes. This gene-specific imaging strategy has the potential to reveal regulatory mechanisms, which would be difficult to imagine outside of single living cells.

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

Cited by 22 publications

References 53 publications

Mitogen-activated Protein Kinase-mediated Licensing of Interferon Regulatory Factor 3/7 Reinforces the Cell Response to Virus

Mitogen-activated Protein Kinase-mediated Licensing of Interferon Regulatory Factor 3/7 Reinforces the Cell Response to Virus

Sp100 Isoform-Specific Regulation of Human Adenovirus 5 Gene Expression

Seeing Is Believing: Visualizing Transcriptional Dynamics in Single Cells

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