Role of Histone Post-Translational Modifications in Inflammatory Diseases

Lin, Yingying; Qiu, Ting; Wei, Guifeng; Que, Yueyue; Wang, Wenxin; Kong, Yichao; Xie, Tian; Chen, Xiabin

doi:10.3389/fimmu.2022.852272

Cited by 35 publications

(35 citation statements)

References 230 publications

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“…[168][169][170][171] When challenged again with the same or a different antigen/pathogen, the chromatin shows increased decondensation, demethylation of DNA, and modifications of histone 3 (H3) such as tri-methylation of lysine 4 (K4; H3K4me3), mono-methylation (H3K4me1), and acetylation of lysine 27 (H3K27ac). 172,173 These epigenetic changes lead to enhanced transcription and translation of immune response factors (Fig. 7).…”

Section: Histone Modificationsmentioning

confidence: 99%

Innate Immune Memory in Macrophages

Maheshwari¹

2023

Newborn

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Macrophages have been recognized as the primary mediators of innate immunity starting from embryonic/fetal development. Macrophagemediated defenses may not be as antigen-specific as adaptive immunity, but increasing information suggests that these responses do strengthen with repeated immunological triggers. The concept of innate memory in macrophages has been described as "trained immunity" or "innate immune memory (IIM). " As currently understood, this cellular memory is rooted in epigenetic and metabolic reprogramming. The recognition of IIM may be particularly important in the fetus and the young neonate who are yet to develop protective levels of adaptive immunity, and could even be of preventive/therapeutic importance in many disorders. There may also be a possibility of therapeutic enhancement with targeted vaccination. This article presents a review of the properties, mechanisms, and possible clinical significance of macrophage-mediated IIM.

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Section: Histone Modificationsmentioning

confidence: 99%

Innate Immune Memory in Macrophages

Maheshwari¹

2023

Newborn

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“…While the associations between individual epigenetic markers and disease states/cellular functions are, themselves, novel, the epigenetic landscape of a cell is governed by the combined effects of diverse post-translational modifications 27 .…”

Section: An Immune Cell-spanning Epigenetic Signature Predicts Diseas...mentioning

confidence: 99%

Disease Tolerance Acquired Through RepeatedPlasmodiumInfection Involves Epigenetic Reprogramming of Innate Immune Cells

Nideffer

Donato

et al. 2023

Preprint

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SummaryThe regulation of inflammation is a critical aspect of disease tolerance and naturally acquired immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by Time-Of-Flight (EpiTOF), that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing—at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also predicted long-term future disease tolerance when observed in uninfected children. This broad methylated signature likely develops gradually and was associated with age and recent parasite exposure. Our data support a model whereby exposure toPlasmodium falciparuminduces epigenetic changes that regulate excessive inflammation and contribute to naturally acquired immunity to malaria.

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“…In general, H3K4, H3K36, and H3K79 methylation is associated with transcriptional activation, while H3K9, H3K27, and H4K20 methylation is linked to transcriptional repression. Aberrations in the deposition of histone PTMs have been associated with a multitude of human diseases, including cancer, neurodegenerative disorders, and cardiac and autoimmune diseases [8][9][10][11]. In cancer, decreased levels of H3K14ac, H4K20me3, and H4K16ac have been reported as common hallmarks of cancer [12,13].…”

Section: Histone Ptms and Histone Modifiersmentioning

confidence: 99%

Proteomics contributions to epigenetic drug discovery

Noberini,

Bonaldi

2023

Proteomics

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The combined activity of epigenetic features, which include histone post‐translational modifications, DNA methylation, and nucleosome positioning, regulates gene expression independently from changes in the DNA sequence, defining how the shared genetic information of an organism is used to generate different cell phenotypes. Alterations in epigenetic processes have been linked with a multitude of diseases, including cancer, fueling interest in the discovery of drugs targeting the proteins responsible for writing, erasing, or reading histone and DNA modifications. Mass spectrometry (MS)‐based proteomics has emerged as a versatile tool that can assist drug discovery pipelines from target validation, through target deconvolution, to monitoring drug efficacy in vivo. Here, we provide an overview of the contributions of MS‐based proteomics to epigenetic drug discovery, describing the main approaches that can be used to support different drug discovery pipelines and highlighting how they contributed to the development and characterization of epigenetic drugs.

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Role of Histone Post-Translational Modifications in Inflammatory Diseases

Cited by 35 publications

References 230 publications

Innate Immune Memory in Macrophages

Innate Immune Memory in Macrophages

Disease Tolerance Acquired Through RepeatedPlasmodiumInfection Involves Epigenetic Reprogramming of Innate Immune Cells

Proteomics contributions to epigenetic drug discovery

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