Histone post-translational modifications — cause and consequence of genome function

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 563 - 580

Published: March 25, 2022

Language: Английский

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The evolving metabolic landscape of chromatin biology and epigenetics

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(12), P. 737 - 753

Published: Sept. 9, 2020

Language: Английский

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Mitochondrial signal transduction

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1620 - 1653

Published: Nov. 1, 2022

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue the processor cell, together with nucleus other they constitute mitochondrial information processing system (MIPS). In a three-step process, (1) sense respond to both endogenous environmental inputs through morphological functional remodeling; (2) integrate network-based physical interactions diffusion mechanisms; (3) produce output signals tune functions systemically regulate physiology. This input-to-output transformation allows metabolic, biochemical, neuroendocrine, local or systemic enhance organismal adaptation. An explicit focus on signal transduction emphasizes role communication in biology. framework also opens new avenues understand how mediate inter-organ processes underlying human health.

Language: Английский

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Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 2, 2023

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism others. The term ‘epigenetics’ was firstly proposed 1942 with the development technologies, exploration epigenetics made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, noncoding RNA (ncRNA), which exert different effects on diseases. Genetic non-genetic factors, ageing, diet, exercise, interact jointly affect formation phenotype. Understanding could be applied diagnosing treating diseases clinic, biomarkers, drugs, editing. In this review, we introduce brief history well milestone events since proposal ‘epigenetics’. Moreover, summarise research methods general mechanisms modulation. Furthermore, interaction between genetic or factors. Finally, clinical trials applications

Language: Английский

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The role of histone modifications: from neurodevelopment to neurodiseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 6, 2022

Abstract Epigenetic regulatory mechanisms, including DNA methylation, histone modification, chromatin remodeling, and microRNA expression, play critical roles in cell differentiation organ development through spatial temporal gene regulation. Neurogenesis is a sophisticated complex process by which neural stem cells differentiate into specialized brain types at specific times regions of the brain. A growing body evidence suggests that epigenetic such as modifications, allow fine-tuning coordination spatiotemporal expressions during neurogenesis. Aberrant modifications contribute to neurodegenerative neuropsychiatric diseases. Herein, recent progress understanding regulating embryonic adult neurogenesis comprehensively reviewed. The implicated diseases are also covered, future directions this area provided.

Language: Английский

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Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity

Science, Journal Year: 2023, Volume and Issue: 379(6637)

Published: March 16, 2023

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, identified panel of cysteine residues differentially modified carboxyethylation required 3-hydroxypropionic acid generate patients with AS. The lysosomal degradation integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated peptides were presented HLA-DRB1*04 stimulate CD4+ T cell responses and induce autoantibody production. Immunization HLA-DR4 transgenic mice the ITGA2B-ceC96 peptide promoted colitis vertebral bone erosion. Thus, metabolite-induced give rise pathogenic lead autoreactive production autoimmune diseases.

Language: Английский

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Disease-associated astrocyte epigenetic memory promotes CNS pathology

Nature, Journal Year: 2024, Volume and Issue: 627(8005), P. 865 - 872

Published: March 20, 2024

Language: Английский

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Bidirectional histone monoaminylation dynamics regulate neural rhythmicity

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles permissive gene expression 1–3 . We previously demonstrated serotonylation 4–10 and dopaminylation 9,11–13 histone (H3Q5ser H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), alter both local global chromatin states. Here we found TG2 additionally functions as eraser exchanger monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic contributes to circadian behaviour. H3Q5his, contrast H3Q5ser, inhibits the binding WDR5, a core member Lys4 (H3K4) methyltransferase complexes, thereby antagonizing activities on H3K4. Taken together, these data elucidate mechanism through single regulatory enzyme has ability sense chemical microenvironments affect states cells, dynamics regulation neural rhythmicity.

Language: Английский

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Nothing Is Yet Set in (Hi)stone: Novel Post-Translational Modifications Regulating Chromatin Function

Trends in Biochemical Sciences, Journal Year: 2020, Volume and Issue: 45(10), P. 829 - 844

Published: June 1, 2020

Language: Английский

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The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 78(6), P. 2517 - 2563

Published: Dec. 2, 2020

Abstract Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum (ASD), are a large group of in which early insults during brain development result wide heterogeneous clinical diagnoses. Mutations genes coding for chromatin remodelers overrepresented NDD cohorts, pointing towards epigenetics as convergent pathogenic pathway between these disorders. In this review we detail the role NDD-associated developmental continuum progenitor expansion, differentiation, cell-type specification, migration maturation. We discuss how defects remodelling time points compound over impaired circuit establishment. particular, focus on their three largest cell populations: glutamatergic neurons, GABAergic glia cells. An in-depth understanding spatiotemporal neurodevelopment can contribute to identification molecular targets treatment strategies.

Language: Английский

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