PHF13: A new player involved in RNA polymerase II transcriptional regulation and co-transcriptional splicing

Fuchs, Alisa; Torroba, Marcos; Kinkley, Sarah

doi:10.1080/21541264.2016.1274813

Cited by 3 publications

(7 citation statements)

References 39 publications

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“…This block is alleviated by Vpr-mediated PHF13 depletion. Of note, the multitude of Vpr effects on several cellular processes [ 7 , 12 , 71 ] could be explained by the depletion of PHF13 and its emerging role in transcriptional regulation and co-transcriptional splicing [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thereby it intriguingly up- and downregulates multiple genes involved in transcriptional regulation, DNA binding and chromatin organization, and cell cycle regulation and differentiation [ 21 ]. In addition, the PHF13 interactome is enriched for approximately 50 spliceosomal proteins [ 22 ]. Altogether, this suggests that PHF13 is a transcriptional co-regulator at H3K4me2/3 that couples transcription with co-transcriptional splicing [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the PHF13 interactome is enriched for approximately 50 spliceosomal proteins [ 22 ]. Altogether, this suggests that PHF13 is a transcriptional co-regulator at H3K4me2/3 that couples transcription with co-transcriptional splicing [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication

et al. 2017

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Viruses interact with multiple host cell factors. Some of these are required to promote viral propagation, others have roles in inhibiting infection. Here, we delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1 restriction factor. Early in the HIV-1 replication cycle PHF13 increased the number of integrated proviral copies and the number of infected cells. However, after HIV-1 integration, high levels of PHF13 suppressed viral gene expression. The antiviral activity of PHF13 is counteracted by the viral accessory protein Vpr, which mediates PHF13 degradation. Altogether, the transcriptional master regulator and chromatin binding protein PHF13 does not have purely repressive effects on HIV-1 replication, but also promotes viral integration. By the functional characterization of the dual role of PHF13 during the HIV-1 replication cycle, we reveal a surprising and intricate mechanism through which HIV-1 might regulate the switch from integration to viral gene expression. Furthermore, we identify PHF13 as a cellular target specifically degraded by HIV-1 Vpr.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication

et al. 2017

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“…This chromatin association is either mediated by the PHD domain or by a centrally located region of SPOC1. SPOC1 is able to directly bind chromatin via H3K4me2/3 interactions and indirectly via the polycomb repressive complex 2 (PRC2) and RNA polymerase II (RNAP II) [ 9 ]. SPOC1 targets genes that are transcriptionally more active and is classified as a H3K4me2/3 reader.…”

Section: Introductionmentioning

confidence: 99%

Discovery of a Novel Antiviral Effect of the Restriction Factor SPOC1 against Human Cytomegalovirus

Kuderna,

Reichel,

Tillmanns

et al. 2024

Viruses

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The chromatin-remodeler SPOC1 (PHF13) is a transcriptional co-regulator and has been identified as a restriction factor against various viruses, including human cytomegalovirus (HCMV). For HCMV, SPOC1 was shown to block the onset of immediate-early (IE) gene expression under low multiplicities of infection (MOI). Here, we demonstrate that SPOC1-mediated restriction of IE expression is neutralized by increasing viral titers. Interestingly, our study reveals that SPOC1 exerts an additional antiviral function beyond the IE phase of HCMV replication. Expression of SPOC1 under conditions of high MOI resulted in severely impaired viral DNA replication and viral particle release, which may be attributed to inefficient viral transcription. With the use of click chemistry, the localization of viral DNA was investigated at late time points after infection. Intriguingly, we detected a co-localization of SPOC1, RNA polymerase II S5P and polycomb repressor complex 2 (PRC2) components in close proximity to viral DNA in areas that are hypothesized to harbor viral transcription sites. We further identified the N-terminal domain of SPOC1 to be responsible for interaction with EZH2, a subunit of the PRC2 complex. With this study, we report a novel and potent antiviral function of SPOC1 against HCMV that is efficient even with unrestricted IE gene expression.

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“…PHF13 is a plant homeodomain (PHD) finger-containing protein that plays an essential role in modulating the cell cycle [ 28 ], DNA damage repair [ 29 ], and chromatin structure [ 28 ]. A recent study found that PHF13 specifically recognizes H3K4me2/3 and functions as a transcription coactivator to facilitate gene transcription [ 30 – 32 ]. Interestingly, PHF13 also interacts with EZH2, a core subunit of the polycomb repressive complex 2 (PRC2), on a particular chromatin region termed “bivalent,” which is co-occupied by the active histone marker H3K4me3 and repressive histone marker H3K27me3 [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

PHF13 epigenetically activates TGFβ driven epithelial to mesenchymal transition

Sun

et al. 2022

Cell Death Dis

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Epigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. In this study, we demonstrate that PHF13 is required for pancreatic-cancer-cell growth and metastasis. Integrative analysis of transcriptome and epigenetic profiles provide further mechanistic insights into the epigenetic regulation of genes associated with cell metastasis during the epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β (TGFβ). Our data suggest PHF13 depletion impairs activation of TGFβ stimulated genes and correlates with a loss of active epigenetic marks (H3K4me3 and H3K27ac) at these genomic regions. These observations argue for a dependency of TGFβ target activation on PHF13. Furthermore, PHF13-dependent chromatin regions are enriched in broad H3K4me3 domains and super-enhancers, which control genes critical to cancer-cell migration and invasion, such as SNAI1 and SOX9. Overall, our data indicate a functional and mechanistic correlation between PHF13 and EMT.

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PHF13: A new player involved in RNA polymerase II transcriptional regulation and co-transcriptional splicing

Cited by 3 publications

References 39 publications

Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication

Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication

Discovery of a Novel Antiviral Effect of the Restriction Factor SPOC1 against Human Cytomegalovirus

PHF13 epigenetically activates TGFβ driven epithelial to mesenchymal transition

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