Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks
Abstract Background Sitting at the interface of gene expression and host-pathogen interaction, polymerase associated factor 1 complex (PAF1C) is a rising player in the innate immune response. The complex localizes to the nucleus and associates with chromatin to modulate RNA polymerase II (RNAPII) el...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-022-09013-6 |
| _version_ | 1811190496772489216 |
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| author | Matthew W. Kenaston Oanh H. Pham Marine J. Petit Priya S. Shah |
| author_facet | Matthew W. Kenaston Oanh H. Pham Marine J. Petit Priya S. Shah |
| author_sort | Matthew W. Kenaston |
| collection | DOAJ |
| description | Abstract Background Sitting at the interface of gene expression and host-pathogen interaction, polymerase associated factor 1 complex (PAF1C) is a rising player in the innate immune response. The complex localizes to the nucleus and associates with chromatin to modulate RNA polymerase II (RNAPII) elongation of gene transcripts. Performing this function at both proximal and distal regulatory elements, PAF1C interacts with many host factors across such sites, along with several microbial proteins during infection. Therefore, translating the ubiquity of PAF1C into specific impacts on immune gene expression remains especially relevant. Results Advancing past work, we treat PAF1 knockout cells with a slate of immune stimuli to identify key trends in PAF1-dependent gene expression with broad analytical depth. From our transcriptomic data, we confirm PAF1 is an activator of traditional immune response pathways as well as other cellular pathways correlated with pathogen defense. With this model, we employ computational approaches to refine how PAF1 may contribute to both gene activation and suppression. Specifically focusing on transcriptional motifs and regulons, we predict gene regulatory elements strongly associated with PAF1, including those implicated in an immune response. Overall, our results suggest PAF1 is involved in innate immunity at several distinct axes of regulation. Conclusions By identifying PAF1-dependent gene expression across several pathogenic contexts, we confirm PAF1C to be a key mediator of innate immunity. Combining these transcriptomic profiles with potential regulatory networks corroborates the previously identified functions of PAF1C. With this, we foster new avenues for its study as a regulator of innate immunity, and our results will serve as a basis for targeted study of PAF1C in future validation studies. |
| first_indexed | 2024-04-11T14:51:02Z |
| format | Article |
| id | doaj.art-d0aee60c52014064846f44eaccebe881 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-11T14:51:02Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-d0aee60c52014064846f44eaccebe8812022-12-22T04:17:27ZengBMCBMC Genomics1471-21642022-11-0123111910.1186/s12864-022-09013-6Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networksMatthew W. Kenaston0Oanh H. Pham1Marine J. Petit2Priya S. Shah3Department of Microbiology and Molecular Genetics, University of CaliforniaDepartment of Microbiology and Molecular Genetics, University of CaliforniaDepartment of Microbiology and Molecular Genetics, University of CaliforniaDepartment of Microbiology and Molecular Genetics, University of CaliforniaAbstract Background Sitting at the interface of gene expression and host-pathogen interaction, polymerase associated factor 1 complex (PAF1C) is a rising player in the innate immune response. The complex localizes to the nucleus and associates with chromatin to modulate RNA polymerase II (RNAPII) elongation of gene transcripts. Performing this function at both proximal and distal regulatory elements, PAF1C interacts with many host factors across such sites, along with several microbial proteins during infection. Therefore, translating the ubiquity of PAF1C into specific impacts on immune gene expression remains especially relevant. Results Advancing past work, we treat PAF1 knockout cells with a slate of immune stimuli to identify key trends in PAF1-dependent gene expression with broad analytical depth. From our transcriptomic data, we confirm PAF1 is an activator of traditional immune response pathways as well as other cellular pathways correlated with pathogen defense. With this model, we employ computational approaches to refine how PAF1 may contribute to both gene activation and suppression. Specifically focusing on transcriptional motifs and regulons, we predict gene regulatory elements strongly associated with PAF1, including those implicated in an immune response. Overall, our results suggest PAF1 is involved in innate immunity at several distinct axes of regulation. Conclusions By identifying PAF1-dependent gene expression across several pathogenic contexts, we confirm PAF1C to be a key mediator of innate immunity. Combining these transcriptomic profiles with potential regulatory networks corroborates the previously identified functions of PAF1C. With this, we foster new avenues for its study as a regulator of innate immunity, and our results will serve as a basis for targeted study of PAF1C in future validation studies.https://doi.org/10.1186/s12864-022-09013-6Polymerase associated factor 1 complex (PAF1C)Innate immunityNetwork analysisGene expressionTranscriptomicsRegulatory motifs |
| spellingShingle | Matthew W. Kenaston Oanh H. Pham Marine J. Petit Priya S. Shah Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks BMC Genomics Polymerase associated factor 1 complex (PAF1C) Innate immunity Network analysis Gene expression Transcriptomics Regulatory motifs |
| title | Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks |
| title_full | Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks |
| title_fullStr | Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks |
| title_full_unstemmed | Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks |
| title_short | Transcriptomic profiling implicates PAF1 in both active and repressive immune regulatory networks |
| title_sort | transcriptomic profiling implicates paf1 in both active and repressive immune regulatory networks |
| topic | Polymerase associated factor 1 complex (PAF1C) Innate immunity Network analysis Gene expression Transcriptomics Regulatory motifs |
| url | https://doi.org/10.1186/s12864-022-09013-6 |
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