Acetyltransferases CBP/p300 Control Transcriptional Switch of β-Catenin and Stat1 Promoting Osteoblast Differentiation
© 2023 American Society for Bone and Mineral Research (ASBMR)..
CREB-binding protein (CBP) (CREBBP) and p300 (EP300) are multifunctional histone acetyltransferases (HATs) with extensive homology. Germline mutations of CBP or p300 cause skeletal abnormalities in humans and mice. However, the precise roles of CBP/p300 in bone homeostasis remain elusive. Here, we report that conditional knockout of CBP or p300 in osteoblasts results in reduced bone mass and strength due to suppressed bone formation. The HAT activity is further confirmed to be responsible for CBP/p300-mediated osteogenesis using A-485, a selective inhibitor of CBP/p300 HAT. Mechanistically, CBP/p300 HAT governs osteogenic gene expression in part through transcriptional activation of β-catenin and inhibition of Stat1. Furthermore, acetylation of histone H3K27 and the transcription factor Foxo1 are demonstrated to be involved in CBP/p300 HAT-regulated β-catenin and Stat1 transcription, respectively. Taken together, these data identify acetyltransferases CBP/p300 as critical regulators that promote osteoblast differentiation and reveal an epigenetic mechanism responsible for maintaining bone homeostasis. © 2023 American Society for Bone and Mineral Research (ASBMR).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research - 38(2023), 12 vom: 29. Dez., Seite 1885-1899 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Linlin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.01.2024 Date Revised 11.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jbmr.4925 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363433465 |
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| 245 | 1 | 0 | |a Acetyltransferases CBP/p300 Control Transcriptional Switch of β-Catenin and Stat1 Promoting Osteoblast Differentiation |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 American Society for Bone and Mineral Research (ASBMR). | ||
| 520 | |a CREB-binding protein (CBP) (CREBBP) and p300 (EP300) are multifunctional histone acetyltransferases (HATs) with extensive homology. Germline mutations of CBP or p300 cause skeletal abnormalities in humans and mice. However, the precise roles of CBP/p300 in bone homeostasis remain elusive. Here, we report that conditional knockout of CBP or p300 in osteoblasts results in reduced bone mass and strength due to suppressed bone formation. The HAT activity is further confirmed to be responsible for CBP/p300-mediated osteogenesis using A-485, a selective inhibitor of CBP/p300 HAT. Mechanistically, CBP/p300 HAT governs osteogenic gene expression in part through transcriptional activation of β-catenin and inhibition of Stat1. Furthermore, acetylation of histone H3K27 and the transcription factor Foxo1 are demonstrated to be involved in CBP/p300 HAT-regulated β-catenin and Stat1 transcription, respectively. Taken together, these data identify acetyltransferases CBP/p300 as critical regulators that promote osteoblast differentiation and reveal an epigenetic mechanism responsible for maintaining bone homeostasis. © 2023 American Society for Bone and Mineral Research (ASBMR) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ACETYLATION | |
| 650 | 4 | |a BONE FORMATION | |
| 650 | 4 | |a CBP/p300 | |
| 650 | 4 | |a OSTEOBLAST DIFFERENTIATION | |
| 650 | 4 | |a STAT1 | |
| 650 | 4 | |a β-CATENIN | |
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| 650 | 7 | |a Stat1 protein, mouse |2 NLM | |
| 650 | 7 | |a STAT1 Transcription Factor |2 NLM | |
| 650 | 7 | |a Crebbp protein, mouse |2 NLM | |
| 650 | 7 | |a EC 2.3.1.48 |2 NLM | |
| 700 | 1 | |a Zhu, Kecheng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jingzun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaojing |e verfasserin |4 aut | |
| 700 | 1 | |a Sheng, Chunxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Deng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yuying |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lihao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Bei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Libin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianmin |e verfasserin |4 aut | |
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