The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA
Copyright © 2024 Elsevier Inc. All rights reserved..
Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Developmental cell - 59(2024), 8 vom: 22. Apr., Seite 991-1009.e12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bi, Shijia [VerfasserIn] |
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| Links: |
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| Themen: |
Aging |
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| Anmerkungen: |
Date Completed 24.04.2024 Date Revised 24.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.devcel.2024.02.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Jiang, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Qianzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zehua |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Si |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ruoqi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zunpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junhang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jianli |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Guoqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zeming |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Zhiqing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Izpisua Belmonte, Juan Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Guang-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Jing |e verfasserin |4 aut | |
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