Reversible histone glycation is associated with disease-related changes in chromatin architecture
| Autor: | Rachel Leicher, Albert S Agustinus, Qingfei Zheng, Bo Liu, Yael David, Adewola Osunsade, Efrat Finkin-Groner, Hannah K. D'Ambrosio, Shixin Liu, Nathaniel D. Omans, Sarat Chandarlapaty |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Glycation End Products
Advanced 0301 basic medicine Glycosylation Science Protein Deglycase DJ-1 General Physics and Astronomy Breast Neoplasms 02 engineering and technology Article General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Histones Pathogenesis Mice 03 medical and health sciences Glycation Cell Line Tumor Tumor Microenvironment Animals Humans Nucleosome Epigenetics lcsh:Science Epigenesis Multidisciplinary biology Chemistry Acetylation General Chemistry Pyruvaldehyde 021001 nanoscience & nanotechnology In vitro Nucleosomes 3. Good health Cell biology Chromatin 030104 developmental biology Histone biology.protein Heterografts Female lcsh:Q 0210 nano-technology Protein Processing Post-Translational |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Cellular proteins continuously undergo non-enzymatic covalent modifications (NECMs) that accumulate under normal physiological conditions and are stimulated by changes in the cellular microenvironment. Glycation, the hallmark of diabetes, is a prevalent NECM associated with an array of pathologies. Histone proteins are particularly susceptible to NECMs due to their long half-lives and nucleophilic disordered tails that undergo extensive regulatory modifications; however, histone NECMs remain poorly understood. Here we perform a detailed analysis of histone glycation in vitro and in vivo and find it has global ramifications on histone enzymatic PTMs, the assembly and stability of nucleosomes, and chromatin architecture. Importantly, we identify a physiologic regulation mechanism, the enzyme DJ-1, which functions as a potent histone deglycase. Finally, we detect intense histone glycation and DJ-1 overexpression in breast cancer tumors. Collectively, our results suggest an additional mechanism for cellular metabolic damage through epigenetic perturbation, with implications in pathogenesis. Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase. |
| Databáze: | OpenAIRE |
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