About this Research Topic
Since its discovery more than 30 years ago, the significance of NF-κB has penetrated virtually all areas of biomedical research. Although the classical role of this critical family of transcription factors has been characterized in the development of the immune system and immunity, NF-κB also regulates cell survival, differentiation and proliferation in a variety of tissues. In fact, dysregulation of NF-κB function has been observed in some of the most devastating diseases such as cancer, autoimmunity and neurodegenerative diseases. A vast amount of data has been generated regarding the factors that regulate NF-κB activity and regarding its numerous target genes in various contexts. Nonetheless, the functional specificity of NF-κB activity is still puzzling, given its ubiquitous expression and induction in response to diverse perturbations from the environment or intracellular stress. Recent advances have shown unexpected complexity regarding the temporal and spatial regulation of NF-κB activity. However, the role of these dynamics in fine-tuning epigenetic and transcriptional programs remains unknown.
In this Research Topic, we welcome the submission of articles (Original Research, Reviews, Technology Reports, Brief Research Reports, Hypothesis and Theory) that illustrate current progress toward elucidating mechanisms of NF-κB-mediated signaling for interpreting pathogens and danger or stress-associated signals and achieving functional specificity with such enigmatic versatility. We particularly welcome immunologically relevant studies which utilize powerful technologies such as (i) advanced microscopy; (ii) high throughput profiling; (iii) epigenomics; (iv) systems biology; (v) CRISPR/Cas genome-editing; (vi) mathematical modeling and (vii) quantitative analyses. These modern tools are constantly evolving and enabling us to address previously intractable questions about the role of NF-κB in the immune system. We aim to showcase recent fruits from their applications in immunologically relevant fundamental topics including:
1. How does NF-κB interact with other transcriptional regulators to elicit stimulus-specific transcriptional responses during immune responses and in the inflammatory state?
2. What signal transduction mechanisms shape NF-κB signaling dynamics and information transfer?
3. New tools to measure and perturb the temporal and spatial dynamics of NF-κB.
4. What is the relationship between complex NF-κB signaling dynamics and functional interpretation of contextual information such as presence of pathogens or stressors?
5. What factors determine whether NF-κB proteins utilize the existing chromatin landscape or shape the epigenome?
6. Most NF-κB binding sites are long linear distance away from promoter targets. How do NF-κB regulated enhancers control the expression of their target genes?
7. How does spatial genome organization affect NF-κB transcriptional activity and how does NF-κB influence higher-order genome configuration which may reinforce immune cell fate or immunological memory?
8. How do ncRNAs interact with the NF-κB regulatory network, particularly in immune cells?
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