MAP2K6 remodels chromatin and facilitates reprogramming by activating Gatad2b-phosphorylation dependent heterochromatin loosening
© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare..
Somatic cell reprogramming is an ideal model for studying epigenetic regulation as it undergoes dramatic chromatin remodeling. However, a role for phosphorylation signaling in chromatin protein modifications for reprogramming remains unclear. Here, we identified mitogen-activated protein kinase kinase 6 (Mkk6) as a chromatin relaxer and found that it could significantly enhance reprogramming. The function of Mkk6 in heterochromatin loosening and reprogramming requires its kinase activity but does not depend on its best-known target, P38. We identified Gatad2b as a novel target of Mkk6 phosphorylation that acts downstream to elevate histone acetylation levels and loosen heterochromatin. As a result, Mkk6 over-expression facilitates binding of Sox2 and Klf4 to their targets and promotes pluripotency gene expression during reprogramming. Our studies not only reveal an Mkk phosphorylation mediated modulation of chromatin status in reprogramming, but also provide new rationales to further investigate and improve the cell fate determination processes.
| Errataetall: |
ErratumIn: Cell Death Differ. 2021 Dec 10;:. - PMID 34893691 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Cell death and differentiation - 29(2022), 5 vom: 23. Mai, Seite 1042-1054 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xing, Guangsuo [VerfasserIn] |
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| Links: |
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| Themen: |
Chromatin |
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| Anmerkungen: |
Date Completed 12.05.2022 Date Revised 02.05.2023 published: Print-Electronic ErratumIn: Cell Death Differ. 2021 Dec 10;:. - PMID 34893691 Citation Status MEDLINE |
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| doi: |
10.1038/s41418-021-00902-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM333527836 |
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| 520 | |a © 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare. | ||
| 520 | |a Somatic cell reprogramming is an ideal model for studying epigenetic regulation as it undergoes dramatic chromatin remodeling. However, a role for phosphorylation signaling in chromatin protein modifications for reprogramming remains unclear. Here, we identified mitogen-activated protein kinase kinase 6 (Mkk6) as a chromatin relaxer and found that it could significantly enhance reprogramming. The function of Mkk6 in heterochromatin loosening and reprogramming requires its kinase activity but does not depend on its best-known target, P38. We identified Gatad2b as a novel target of Mkk6 phosphorylation that acts downstream to elevate histone acetylation levels and loosen heterochromatin. As a result, Mkk6 over-expression facilitates binding of Sox2 and Klf4 to their targets and promotes pluripotency gene expression during reprogramming. Our studies not only reveal an Mkk phosphorylation mediated modulation of chromatin status in reprogramming, but also provide new rationales to further investigate and improve the cell fate determination processes | ||
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| 700 | 1 | |a Huang, Luyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Danyun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Linpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yanshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Zhihong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jianghuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shiting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jieying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiekai |e verfasserin |4 aut | |
| 700 | 1 | |a Pei, Duanqing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xingguo |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Keshi |e verfasserin |4 aut | |
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