Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

Cruz, Cristina; Rosa, Monica Della; Krueger, Christel; Gao, Qian; Field, Lucy; Houseley, Jonathan

doi:10.1101/238048

Cited by 8 publications

(9 citation statements)

References 86 publications

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“…Notably, 30% of H3K4me3-occupied genes displayed a substantial aging-related deregulation [ 56 ]. In agreement with those studies, H3K4me3 levels declined during aging in yeast and the authors described that its loss was linked to the induction of various aging-associated genes [ 57 ].…”

Section: Epigenetics Of Aging and Aging-related Diseasessupporting

confidence: 82%

Epigenetics of Aging and Aging-Associated Diseases

Saul

Kosinsky

2021

IJMS

150

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Aging represents the multifactorial decline in physiological function of every living organism. Over the past decades, several hallmarks of aging have been defined, including epigenetic deregulation. Indeed, multiple epigenetic events were found altered across different species during aging. Epigenetic changes directly contributing to aging and aging-related diseases include the accumulation of histone variants, changes in chromatin accessibility, loss of histones and heterochromatin, aberrant histone modifications, and deregulated expression/activity of miRNAs. As a consequence, cellular processes are affected, which results in the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, and neurodegenerative disorders. In this review, we focus on epigenetic mechanisms underlying aging-related processes in various species and describe how these deregulations contribute to human diseases.

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Section: Epigenetics Of Aging and Aging-related Diseasessupporting

confidence: 82%

Epigenetics of Aging and Aging-Associated Diseases

Saul

Kosinsky

2021

IJMS

150

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“…The role of H3K4me3 in lifespan regulation is controversial and conflicting results have been obtained with several model organisms. Yeast set1 mutants are short-lived in both replicative and 4 chronological aging paradigms (31)(32)(33). Set1-dependent H3K4me3 promotes chronological longevity in yeast by preventing apoptosis and histone loss, and the mark also contributes to the maintenance of transcriptional patterns required for a normal replicative lifespan (31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

“…Yeast set1 mutants are short-lived in both replicative and 4 chronological aging paradigms (31)(32)(33). Set1-dependent H3K4me3 promotes chronological longevity in yeast by preventing apoptosis and histone loss, and the mark also contributes to the maintenance of transcriptional patterns required for a normal replicative lifespan (31)(32)(33). Conversely, partial lossof-function mutations or knockdown of genes encoding the SET1/COMPASS components SET-2, WDR-5, and ASH-2 in C. elegans have been shown to extend lifespan through changes in lipid metabolism triggered by the germline (34,35).…”

Section: Introductionmentioning

confidence: 99%

Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans

Caron

Gely

Garvis

et al. 2021

Preprint

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Post-translational modification of histones, particularly lysine methylation, are thought to play a crucial role in the aging process. Histone 3 lysine 4 (H3K4) methylation, a modification associated with active chromatin, is mediated by a family of SET1 methyltransferases acting within conserved multiprotein complexes known as COMPASS. Previous work in model organisms with partial or complete deletion of COMPASS subunits has yielded conflicting results about the requirement for H3K4 methylation during aging. Here, we reassessed the role of SET1/COMPASS-dependent H3K4 methylation in Caenorhabditis elegans lifespan regulation and fertility by generating set-2(syb2085) mutant animals that express a catalytically inactive form of SET-2, the C. elegans homolog of SET1. We show that animals bearing catalytically inactive SET-2 retain the ability to form COMPASS complexes but have a marked global loss of H3K4 dimethylation and trimethylation. Consistent with previous work, reduced H3K4 methylation was accompanied by loss of fertility; however, in striking contrast to earlier studies, set-2(syb2085) mutants displayed a significantly shortened, not extended, lifespan and had normal intestinal fat stores. Furthermore, other commonly used set-2 mutants were also short-lived, as was a cfp-1 mutant that lacks a non-catalytic SET1/COMPASS component and displays reduced H3K4 methylation. These results challenge previously held views and establish that wild-type H3K4 methylation levels are necessary to achieve a normal lifespan in C. elegans.

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“…In 2010, two investigations reported a high density of histone acetylation and RNAPII, and thus, significant transcriptional activity at certain promoters in activated macrophages and dendritic cells. The primary arm of pathogen recognition, TLRs are usually marked with H3K4me3 [2], a transcription-activating histone modification, denoting trimethylation at the fourth lysine residue of histone H3 [21].…”

Section: Histone Modifications: the Perplexing Epigenetic Circuit Behind Immune Response To Sars-cov-2mentioning

confidence: 99%

Epigenomics in COVID-19; the Link Between DNA Methylation, Histone Modifications and SARS-CoV-2 Infection

Shirvaliloo

2021

Epigenomics

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Epigenomics is the collective study of all epigenetic modifications that can affect the genome, the most pivotal of which are DNA methylation (DNAm), histone modifications (e.g., acetylation, citrullination and phosphorylation) and nucleosome remodeling. The latter refers to the dynamic reorganization in the spatial arrangement of chromatin by means of repositioning the nucleosomes, which are short segments of DNA, consisting of approximately 200 base pairs, coiled around eight histone proteins. The resulting alterations in the structure of these bead-like complexes may favor or oppose transcription, determining the course of disease pathogenesis [1], such as coronavirus disease 2019 . Known to correlate inversely with gene expression, DNAm might be associated with increased susceptibility of the pulmonary tissue to COVID-19 [2] and a higher predisposition to this viral disease in patients with pancreatic [3] and prostate cancer [4]. A lesser known epigenetic mechanism, 'X inactivation' is thought to be connected with the function of innate immunity against COVID-19, particularly in male patients [5]. Furthermore, immunity is also influenced by the extensively diverse histone modifications, especially histone citrullination [6]. Nucleosome remodeling, mediated by contextually important proteins such as SMARCA4 and SMAD3, is another epigenetic mechanism that can affect the course of disease, assuming a patient-wise unfavorable role in the case of COVID-19 [7]. The footprint of epigenomics can even be traced back to prenatal life, when developmentally crucial genes such as PEG10 and ECE1, can be affected by DNAm in response to maternal COVID-19 [8], indicating the overall significance of epigenetics in the recent viral pandemic. COVID-19: unwelcome infection facilitated by epigenetic modificationsA consequence of SARS coronavirus 2 (SARS-CoV-2) infection, COVID-19 is perhaps the greatest health issue of the century, affecting more than 45 million individuals, with a global death toll exceeding one million [7]. The recent, less-anticipated advent of novel SARS-CoV-2 variants with altered Spike proteins, including the strain with 'Spike N453Y' mutation reported in Netherlands and Denmark; and the more overwhelming variants with 'Spike D614G' and 'N501Y' mutations spreading in England, has caused concerns regarding the efficacy of the recently approved vaccines in the future. The N501Y variant, in particular, has been suggested to be 56% more transmissible, owing to the enhanced binding affinity of the Spike protein to its polypeptide receptor, ACE2, on the host cell [9]; a finding with potential epigenetic implications.Containing a positive-sense ssRNA, SARS-CoV-2 is an enveloped β-coronavirus coated with Spike protein on its surface, which relies on the interaction between this protein and the transmembrane ACE2 on the host cell for viral entry. The epigenetic modifications, especially DNAm, regulating the expression of ACE2 had been known well before the emergence of SARS-CoV-2 [2].Nonetheless, the rising prominenc...

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Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

Cited by 8 publications

References 86 publications

Epigenetics of Aging and Aging-Associated Diseases

Epigenetics of Aging and Aging-Associated Diseases

Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans

Epigenomics in COVID-19; the Link Between DNA Methylation, Histone Modifications and SARS-CoV-2 Infection

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