2. Academic Validation
  3. Acetyltransferases CBP/p300 control transcriptional switch of β-catenin and Stat1 promoting osteoblast differentiation

Acetyltransferases CBP/p300 control transcriptional switch of β-catenin and Stat1 promoting osteoblast differentiation

  • J Bone Miner Res. 2023 Oct 18. doi: 10.1002/jbmr.4925.
Linlin Zhang # 1 2 3,  Kecheng Zhu # 1 2,  Jingzun Xu 1 2,  Xiaojing Chen 1 2,  Chunxiang Sheng 1 2,  Deng Zhang 1 2,  Yuying Yang 1 2,  Lihao Sun 1 2,  Hongyan Zhao 1 2,  Xiao Wang 1 2,  Bei Tao 1 2,  Libin Zhou 1 2,  Jianmin Liu 1 2
Affiliations

Affiliations

  • 1 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • # Contributed equally.
PMID: 37850815 DOI: 10.1002/jbmr.4925
Abstract

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. This article is protected by copyright. All rights reserved.

Keywords

CBP/p300; Stat1; acetylation; bone formation; osteoblast differentiation; β-catenin.

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