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Research: Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding
- Liangxi Wang,
- Tiegh Taylor,
- Kumaragurubaran Rathnakumar,
- Nadiya Khyzha,
- Minggao Liang,
- Azad Alizada,
- Laura F. Campitelli,
- Sara E. Pour,
- Zain M. Patel,
- Lina Antounians,
- Ian C. Tobias,
- Huayun Hou,
- Timothy R. Hughes,
- Sushmita Roy,
- Jennifer A. Mitchell,
- Jason E. Fish,
- and Michael D. Wilson
Genome Res. July 2025 35: 1544-1559; Published in Advance June 6, 2025, doi:10.1101/gr.280357.124
...and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we perform a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF...
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Research: Nascent transcript analysis of glucocorticoid crosstalk with TNF defines primary and cooperative inflammatory repression
- Sarah K. Sasse,
- Margaret Gruca,
- Mary A. Allen,
- Vineela Kadiyala,
- Tengyao Song,
- Fabienne Gally,
- Arnav Gupta,
- Miles A. Pufall,
- Robin D. Dowell,
- and Anthony N. Gerber
Genome Res. November 2019 29: 1753-1765; Published in Advance September 13, 2019, doi:10.1101/gr.248187.119
...relative to vehicle (for examples, see Fig. 3, B and C). As NF-kB exhibits minimal basal occupancy in BEAS-2B cells (Kadiyala et al. 2016), these data do not support a singular mechanistic role for repressive tethering between the GR and NF-kB as the basis for dex-mediated repression of TNF signaling...
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Research: Acute TNF-induced repression of cell identity genes is mediated by NFκB-directed redistribution of cofactors from super-enhancers
- Søren Fisker Schmidt,
- Bjørk Ditlev Larsen,
- Anne Loft,
- Ronni Nielsen,
- Jesper Grud Skat Madsen,
- and Susanne Mandrup
Genome Res. September 2015 25: 1281-1294; Published in Advance June 25, 2015, doi:10.1101/gr.188300.114
...that, with high accuracy, predict which enhancers and genes are repressed by TNF in adipocytes. We show that these models are applicable to other cell types where TNF represses genes associated with super-enhancers in a highly cell-type–specific manner. Our results propose a novel paradigm for NFκB-mediated...
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METHODS: Computationally Identifying Novel NF-κB-Regulated Immune Genes in the Human Genome
- Rongxiang Liu,
- Richard C. McEachin,
- and David J. States
Genome Res. April 1, 2003 13: 654-661; Published in Advance March 12, 2003, doi:10.1101/gr.911803
...Consortium 2001 ; Venter et al. 2001 ), and it is estimated that there are about 35,000 genes in the human . More than half of these genes are novel, and it is reasonable to hypothesize that some of these novel genes have immune functions. Because of the importance of NF-κB signaling in the immune system...
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Method: Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet
- Chuanyuan Wang and
- Zhi-Ping Liu
Genome Res. February 2025 35: 340-354; Published in Advance December 18, 2024, doi:10.1101/gr.279551.124
...on the proinflammatory cytokine TNF during immune responses is well documented, and MAP3K8, another key player in our findings, is crucial for TNF production (Gantke et al. 2011; Huang et al. 2012; Chen et al. 2020; Wang et al. 2020). MAP3K8 participates in T helper cell differentiation and intracellular gene regulation...
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Research: Transcriptional programs mediating neuronal toxicity and altered glial–neuronal signaling in a Drosophila knock-in tauopathy model
- Hassan Bukhari,
- Vanitha Nithianandam,
- Rachel A. Battaglia,
- Anthony Cicalo,
- Souvarish Sarkar,
- Aram Comjean,
- Yanhui Hu,
- Matthew J. Leventhal,
- Xianjun Dong,
- and Mel B. Feany
Genome Res. April 2024 34: 590-605; Published in Advance April 10, 2024, doi:10.1101/gr.278576.123
...by expression of ds ligand and fat receptor, is up-regulated in astrocytes of flies expressing P251L mutant Tau compared with controls. (G,H) Predicted TNF-α signaling from ligand eiger to receptor wengen is increased in astrocytes of Tau P251L knock-in flies. In panels B,D,F,H, the interactions from...
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Method: Accurate estimation of pathway activity in single cells for clustering and differential analysis
- Daniel Davis,
- Avishai Wizel,
- and Yotam Drier
Genome Res. June 2024 34: 925-936; Published in Advance July 9, 2024, doi:10.1101/gr.278431.123
...(Liu et al. 2021). TGF beta signaling also activates TNF signaling via NF-kB in glioblastoma, which in turn induces mesenchymal transition (Bhat et al. 2013; Yan et al. 2022). Furthermore, these works also suggest that these two pathways can be targeted to improve overall survival and specifically...
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Method: Identification of phenotype-specific networks from paired gene expression–cell shape imaging data
- Charlie George Barker,
- Eirini Petsalaki,
- Girolamo Giudice,
- Julia Sero,
- Emmanuel Nsa Ekpenyong,
- Chris Bakal,
- and Evangelia Petsalaki
Genome Res. April 2022 32: 750-765; Published in Advance February 23, 2022, doi:10.1101/gr.276059.121
...that is observed to decrease in mesenchymal-like cell shapes (Dai et al. 2015). Other modules whose expression distinguishes basal-like from luminal-like include the MAL2-AS1 module (enriched in desmosome assembly), ARNT/KO module (enriched in TNF-signaling by NF-kB), and ECM organization module (enriched in focal...
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Method: High-throughput characterization of genetic effects on DNA–protein binding and gene transcription
- Cynthia A. Kalita,
- Christopher D. Brown,
- Andrew Freiman,
- Jenna Isherwood,
- Xiaoquan Wen,
- Roger Pique-Regi,
- and Francesca Luca
Genome Res. November 2018 28: 1701-1708; Published in Advance September 25, 2018, doi:10.1101/gr.237354.118
...functions as a cytoplasmic attenuator of NF-κB signaling in the repression of myeloid tumors. Blood 118: 6626–6637. ↵Nédélec Y, Sanz J, Baharian G, Szpiech ZA, Pacis A, Dumaine A, Grenier JC, Freiman A, Sams AJ, Hebert S, et al. 2016. Genetic ancestry and natural selection drive population differences...
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Research: Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma
- Raquel Ordoñez,
- Marta Kulis,
- Nuria Russiñol,
- Vicente Chapaprieta,
- Arantxa Carrasco-Leon,
- Beatriz García-Torre,
- Stella Charalampopoulou,
- Guillem Clot,
- Renée Beekman,
- Cem Meydan,
- Martí Duran-Ferrer,
- Núria Verdaguer-Dot,
- Roser Vilarrasa-Blasi,
- Paula Soler-Vila,
- Leire Garate,
- Estíbaliz Miranda,
- Edurne San José-Enériz,
- Juan R. Rodriguez-Madoz,
- Teresa Ezponda,
- Rebeca Martínez-Turrilas,
- Amaia Vilas-Zornoza,
- David Lara-Astiaso,
- Daphné Dupéré-Richer,
- Joost H.A. Martens,
- Halima El-Omri,
- Ruba Y. Taha,
- Maria J. Calasanz,
- Bruno Paiva,
- Jesus San Miguel,
- Paul Flicek,
- Ivo Gut,
- Ari Melnick,
- Constantine S. Mitsiades,
- Jonathan D. Licht,
- Elias Campo,
- Hendrik G. Stunnenberg,
- Xabier Agirre,
- Felipe Prosper,
- and Jose I. Martin-Subero
Genome Res. September 2020 30: 1217-1227; Published in Advance August 20, 2020, doi:10.1101/gr.265520.120
...signaling pathways, such as NF-kB signaling, MTOR signaling, the TP53 pathway, and the NOTCH pathway, as well as oxidative stress responses (Fig. 2E). Figure 2, F through H, shows examples of genes with regulatory elements becoming de novo active in MM as compared to normal cells. For instance, in the case...
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