Epigenetic regulation of the innate immune response to infection

Zhang, Qian; Cao, Xuetao

doi:10.1038/s41577-019-0151-6

Cited by 275 publications

(236 citation statements)

References 168 publications

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“…Our results add important and complementary information to existing data showing the importance of the chromatin landscape at promoters including nucleosome position, localization of regulatory factors and histone post-translational modifications. The data we show here expounds upon the interplay between chromatin structure to function, which is consonant with models suggested by preeminent immunologists (Natoli 2010, Cuartero et al, 2018, Zhang and Cao 2019). In aggregate, our results suggest that chromatin structure plays a functional role in the dynamic immune response and that nucleosome sensitivity indicates the regulatory potential of specific loci that are poised for the appropriate genomic response.…”

Section: Discussionsupporting

confidence: 88%

MNase profiling of promoter chromatin inS. typhimurium-stimulated GM12878 cells reveals dynamic and response-specific nucleosome architecture

Cole

Dennis

2019

Preprint

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The nucleosome is the primary unit of chromatin structure and commonly imputed as a regulator of nuclear events, although the exact mechanisms remain unclear. Recent studies have shown that certain nucleosomes can have different sensitivities to micrococcal nuclease (MNase) digestion, resulting in the release of populations of nucleosomes dependent on the concentration of MNase. Mapping MNase sensitivity of nucleosomes at transcription start sites genome-wide reveals an important functional nucleosome organization that correlates with gene expression levels and transcription factor binding. In order to understand nucleosome distribution and sensitivity dynamics during a robust genome response, we mapped nucleosome position and sensitivity using multiple concentrations of MNase. We use the innate immune response as a model system to understand chromatin-mediated regulation. Herein we demonstrate that stimulation of a human lymphoblastoid cell line (GM12878) with heat-killed Salmonella typhimurium (HKST) results in widespread nucleosome remodeling of response-specific loci. We further show that the response alters the sensitivity of promoter nucleosomes. Finally, we correlate the increased sensitivity with response-specific transcription factor binding. These results indicate that nucleosome distribution and sensitivity dynamics are integral to appropriate cellular response and pave the way for further studies that will deepen our understanding of the specificity of genome response.

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Section: Discussionsupporting

confidence: 88%

MNase profiling of promoter chromatin inS. typhimurium-stimulated GM12878 cells reveals dynamic and response-specific nucleosome architecture

Cole

Dennis

2019

Preprint

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“…4). Lastly, miRNAs and lncRNAs modulate interferon-dependent and ISG-dependent innate immune responses by multiple pattern-recognition receptors, including RLRs, through broader mechanisms, such as chromatin remodelling (reviewed in detail elsewhere 149 ).…”

Section: Regulation By Non-coding Rnas Cellular Non-codingmentioning

confidence: 99%

RIG-I-like receptors: their regulation and roles in RNA sensing

2020

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| Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key sensors of virus infection, mediating the transcriptional induction of type I interferons and other genes that collectively establish an antiviral host response. Recent studies have revealed that both viral and host-derived RNAs can trigger RLR activation; this can lead to an effective antiviral response but also immunopathology if RLR activities are uncontrolled. In this Review , we discuss recent advances in our understanding of the types of RNA sensed by RLRs in the contexts of viral infection, malignancies and autoimmune diseases. We further describe how the activity of RLRs is controlled by host regulatory mechanisms, including RLR-interacting proteins, post-translational modifications and non-coding RNAs. Finally , we discuss key outstanding questions in the RLR field, including how our knowledge of RLR biology could be translated into new therapeutics.

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“…Inappropriate expression and activation of innate sensors will induce serious autoimmune diseases. 80,81 Thus, the activation of nu- Various studies demonstrate that the proteasomal degradation of innate sensors after K48-linked polyubiquitination is a crucial negative regulation of innate immune response. 83 For instance, at the late stages of viral infection, the protein levels of E3 ubiquitin ligases RNF122 and RNF125 increase, which directly mediates the K48-linked polyubiquitination of RIG-I, leading to the proteasomal degradation of RIG-I.…”

Section: Reg Ul Ati On Of N Ucle Ar Innate S Ensor S Ig Nalingmentioning

confidence: 99%

Nuclear innate sensors for nucleic acids in immunity and inflammation

Lin

Cao

2020

Immunological Reviews

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Innate sensors recognize pathogen‐associated molecular patterns (PAMPs) or damage‐associated molecular patterns (DAMPs) to initiate innate immune response by activating downstream signaling. These evolutionarily conserved innate sensors usually locate in the plasma membrane or cytoplasm. However, the nucleus‐localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. Furthermore, these nuclear innate sensors evolve varied mechanisms for discriminating self from non‐self nucleic acids to maintain immune homeostasis and avoid autoinflammatory immune response. In this review, we summarize the recent findings on the identification of nuclear innate sensors for nucleic acids, such as hnRNPA2B1, IFI16, SAFA, and their roles in host defense and inflammatory response.

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Epigenetic regulation of the innate immune response to infection

Cited by 275 publications

References 168 publications

MNase profiling of promoter chromatin inS. typhimurium-stimulated GM12878 cells reveals dynamic and response-specific nucleosome architecture

MNase profiling of promoter chromatin inS. typhimurium-stimulated GM12878 cells reveals dynamic and response-specific nucleosome architecture

RIG-I-like receptors: their regulation and roles in RNA sensing

Nuclear innate sensors for nucleic acids in immunity and inflammation

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