The role of histone H3 leucine 126 in fine-tuning the copper reductase activity of nucleosomes DOI Creative Commons

Nataliya P. Tod,

Maria Vogelauer, Chen Cheng

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(6), P. 107314 - 107314

Published: April 22, 2024

The copper reductase activity of histone H3 suggests undiscovered characteristics within the protein. Here, we investigated function leucine 126 (H3L126), which occupies an axial position relative to binding. Typically found as a methionine or in binding proteins, ligand influences reduction potential bound ion, modulating its tendency accept yield electrons. We that mutation H3L126 (H3L126M) enhanced enzymatic native yeast nucleosomes vitro and increased intracellular levels Cu1+, leading improved copper-dependent activities including mitochondrial respiration growth oxidative media with low copper. Conversely, histidine (H3L126H) decreased nucleosome's adversely affected vivo. Our findings demonstrate fine-tunes highlight utility nucleosome novel paradigm uncover previously unnoticed features histones.

Language: Английский

Crosstalk between metabolism and epigenetics during macrophage polarization DOI Creative Commons
Kangling Zhang, Chinnaswamy Jagannath

Epigenetics & Chromatin, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 29, 2025

Macrophage polarization is a dynamic process driven by complex interplay of cytokine signaling, metabolism, and epigenetic modifications mediated pathogens. Upon encountering specific environmental cues, monocytes differentiate into macrophages, adopting either pro-inflammatory (M1) or anti-inflammatory (M2) phenotype, depending on the cytokines present. M1 macrophages are induced interferon-gamma (IFN-γ) characterized their reliance glycolysis role in host defense. In contrast, M2 stimulated interleukin-4 (IL-4) interleukin-13 (IL-13), favor oxidative phosphorylation participate tissue repair responses. Metabolism tightly linked to regulation, because key metabolic intermediates such as acetyl-coenzyme A (CoA), α-ketoglutarate (α-KG), S-adenosylmethionine (SAM), nicotinamide adenine dinucleotide (NAD+) serve cofactors for chromatin-modifying enzymes, which turn, directly influences histone acetylation, methylation, RNA/DNA protein arginine methylation. These control gene expression regulating chromatin accessibility, thereby modulating macrophage function polarization. Histone acetylation generally promotes more open structure conducive activation, while methylation can activate repress residue its state. Crosstalk between modifications, further fine-tunes phenotypes transcriptional networks response cues. While primarily functions epigenetics through degradation methylated proteins releases derivatives like asymmetric dimethylarginine (ADMA), contribute metabolism-a factor This review explores intricate relationships metabolism regulation during better understanding this crosstalk will likely generate novel therapeutic insights manipulating infections tuberculosis inflammatory diseases diabetes.

Language: Английский

Citations

2
The SWI/SNF chromatin remodeling complex: a critical regulator of metabolism DOI Creative Commons
Michael Church,

Jerry L. Workman

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(3), P. 1327 - 1337

Published: April 26, 2024

The close relationship between chromatin and metabolism has been well-studied in recent years. Many metabolites have found to be cofactors used modify chromatin, these modifications can turn affect gene transcription. One chromatin-associated factor responsible for regulating transcription is the SWI/SNF complex, an ATP-dependent remodeler conserved throughout eukaryotes. was originally described yeast as genes involved carbon source mating type switching, its mammalian counterpart extensively studied role diseases such cancer. complex closely associated with activation of stress response genes, many which metabolic functions. It now recognized that this a function work shown also key regulator Emerging evidence suggests loss introduces vulnerabilities cells due influence, may present opportunities treatment SWI/SNF-deficient cancers.

Language: Английский

Citations

4
Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders DOI Creative Commons
Benjamin H. Weekley,

Newaz I. Ahmed,

Ian Maze

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 112092 - 112092

Published: Feb. 22, 2025

The evolving field of neuroepigenetics provides important insights into the molecular foundations brain function. Novel sequencing technologies have identified patient-specific mutations and gene expression profiles involved in shaping epigenetic landscape during neurodevelopment disease. Traditional methods to investigate consequences chromatin-related provide valuable phenotypic but often lack information on biochemical mechanisms underlying these processes. Recent studies, however, are beginning elucidate how structural and/or functional aspects histone, DNA, RNA post-translational modifications affect transcriptional landscapes neurological phenotypes. Here, we review identification regulators from genomic studies disease, as well mechanistic findings that reveal intricacies neuronal chromatin regulation. We then discuss serve a guideline for future investigations. end by proposing roadmap therapies exploit coupling them recent advances targeted therapeutics.

Language: Английский

Citations

0
Phospholipid Biosynthesis: An Unforeseen Modulator of Nuclear Metabolism DOI
Hong Qiu, Cunqi Ye

Biology of the Cell, Journal Year: 2025, Volume and Issue: 117(3)

Published: March 1, 2025

ABSTRACT Glycerophospholipid biosynthesis is crucial not only for providing structural components required membrane biogenesis during cell proliferation but also facilitating remodeling under stress conditions. The biosynthetic pathways glycerophospholipid tails, glycerol backbones, and diverse head group classes intersect with various other metabolic processes, sharing intermediary metabolites. Recent studies have revealed intricate connections between synthesis nuclear metabolism, including metabolite‐mediated crosstalk the epigenome, signaling that govern genome integrity, CTP‐involved regulation of nucleotide antioxidant biosynthesis. This review highlights recent advances in understanding functional roles beyond their functions budding yeast mammalian cells. We propose plays an integrative role regulation, a new perspective on lipid biology.

Language: Английский

Citations

0
A two-way relationship between histone acetylation and metabolism DOI
Evelina Charidemou, Antonis Kirmizis

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

2
The role of histone H3 leucine 126 in fine-tuning the copper reductase activity of nucleosomes DOI Creative Commons

Nataliya P. Tod,

Maria Vogelauer, Chen Cheng

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(6), P. 107314 - 107314

Published: April 22, 2024

The copper reductase activity of histone H3 suggests undiscovered characteristics within the protein. Here, we investigated function leucine 126 (H3L126), which occupies an axial position relative to binding. Typically found as a methionine or in binding proteins, ligand influences reduction potential bound ion, modulating its tendency accept yield electrons. We that mutation H3L126 (H3L126M) enhanced enzymatic native yeast nucleosomes vitro and increased intracellular levels Cu1+, leading improved copper-dependent activities including mitochondrial respiration growth oxidative media with low copper. Conversely, histidine (H3L126H) decreased nucleosome's adversely affected vivo. Our findings demonstrate fine-tunes highlight utility nucleosome novel paradigm uncover previously unnoticed features histones.

Language: Английский

Citations

1