DNA methylation and histone variants in aging and cancer

Mangelinck, Adèle; Mann, Carl

doi:10.1016/bs.ircmb.2021.06.002

Cited by 24 publications

(13 citation statements)

References 471 publications

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“…Naked as well as protein-bound mtDNA molecules are potent activators of Toll-like receptor 9 (TLR9) and advanced glycosylation end product-specific receptor (AGER; also known as RAGE) 96 , 97 , two PRRs that are abundantly expressed in the endosomal compartment of myeloid cells (notably neutrophils) 13 . Naked mtDNA largely functions as a TLR9 agonist 96 , reflecting the limited methylation of CpG islands found in the mitochondrial genome 98 and hence its considerable similarity to bacterial DNA (the prototypical TLR9 activator) 99 . Conversely, mtDNA complexed with TFAM or HMGB1, which relocalizes from the nucleus to the cytosol in the course of various stress responses (including inflammasome activation) 100 , has immunostimulatory effects upon binding to TLR9 or AGER 97 , 101 .…”

Section: Mtdamp Signalling Pathwaysmentioning

confidence: 99%

Mitochondrial control of inflammation

et al. 2022

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Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal of permeabilized mitochondria. However, when the homeostatic capacity of such systems is exceeded or when such systems are defective, inflammatory reactions elicited by mitochondria can become pathogenic and contribute to the aetiology of human disorders linked to autoreactivity. In addition, inefficient inflammatory pathways induced by mitochondrial DAMPs can be pathogenic as they enable the establishment or progression of infectious and neoplastic disorders. Here we discuss the molecular mechanisms through which mitochondria control inflammatory responses, the cellular pathways that are in place to control mitochondria-driven inflammation and the pathological consequences of dysregulated inflammatory reactions elicited by mitochondrial DAMPs.

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Section: Mtdamp Signalling Pathwaysmentioning

confidence: 99%

Mitochondrial control of inflammation

et al. 2022

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“…Histone variants often have specialized functions [3]. Mammals have eleven H1 variants, nine H2A variants, five H3 variants, at least two testis-specific H2B variants, and one H4 variant [4].…”

Section: Introductionmentioning

confidence: 99%

Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells

Redon

Schmal

Tewary

et al. 2021

Genes

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H2A.J is a poorly studied mammalian-specific variant of histone H2A. We used immunohistochemistry to study its localization in various human and mouse tissues. H2A.J showed cell-type specific expression with a striking enrichment in luminal epithelial cells of multiple glands including those of breast, prostate, pancreas, thyroid, stomach, and salivary glands. H2A.J was also highly expressed in many carcinoma cell lines and in particular, those derived from luminal breast and prostate cancer. H2A.J thus appears to be a novel marker for luminal epithelial cancers. Knocking-out the H2AFJ gene in T47D luminal breast cancer cells reduced the expression of several estrogen-responsive genes which may explain its putative tumorigenic role in luminal-B breast cancer.

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“…Thus, it could control the expression of genes in the organism. Abnormal methylation of genes is an important factor in the development of cancer (Mangelinck and Mann 2021 ). DNA methylation is also involved in the regulation of respiratory health.…”

Section: Discussionmentioning

confidence: 99%