Metabolic regulation of telomere silencing by SESAME complex-catalyzed H3T11 phosphorylation
| Autor: | Yuan Zhang, Shihao Zhang, Xiangyan Xue, Zitong Zha, Jerry L. Workman, Madelaine Gogol, Xilan Yu, Qi Yu, Shanshan Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Heterochromatin Science Pyruvate Kinase Regulator General Physics and Astronomy Multienzyme complexes Saccharomyces cerevisiae Biology General Biochemistry Genetics and Molecular Biology Article Histones 03 medical and health sciences Sirtuin 2 Chromosomal Instability Gene Expression Regulation Fungal Gene expression Autophagy Serine Gene silencing Phosphorylation Silent Information Regulator Proteins Saccharomyces cerevisiae Multidisciplinary 030102 biochemistry & molecular biology General Chemistry Telomere Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology Histone Telomeres Proteolysis biology.protein |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Telomeres are organized into a heterochromatin structure and maintenance of silent heterochromatin is required for chromosome stability. How telomere heterochromatin is dynamically regulated in response to stimuli remains unknown. Pyruvate kinase Pyk1 forms a complex named SESAME (Serine-responsive SAM-containing Metabolic Enzyme complex) to regulate gene expression by phosphorylating histone H3T11 (H3pT11). Here, we identify a function of SESAME in regulating telomere heterochromatin structure. SESAME phosphorylates H3T11 at telomeres, which maintains SIR (silent information regulator) complex occupancy at telomeres and protects Sir2 from degradation by autophagy. Moreover, SESAME-catalyzed H3pT11 directly represses autophagy-related gene expression to further prevent autophagy-mediated Sir2 degradation. By promoting H3pT11, serine increases Sir2 protein levels and enhances telomere silencing. Loss of H3pT11 leads to reduced Sir2 and compromised telomere silencing during chronological aging. Together, our study provides insights into dynamic regulation of silent heterochromatin by histone modifications and autophagy in response to cell metabolism and aging. Pyruvate kinase phosphorylates histone H3T11 (H3pT11) and represses gene expression by forming a large complex SESAME (Serine-responsive SAM-containing Metabolic Enzyme). Here the authors show that SESAME-catalyzed H3pT11 regulates telomere silencing by promoting Sir2 binding at telomeres and preventing autophagy-mediated Sir2 degradation. |
| Databáze: | OpenAIRE |
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