P300 regulates histone crotonylation and preimplantation embryo development

Di Gao, Chao Li, Shao-Yuan Liu, Teng-Teng Xu, Xiao-Ting Lin, Yong-Peng Tan, Fu-Min Gao, Li-Tao Yi, Jian V. Zhang, Jun-Yu Ma, Tie-Gang Meng, William S. B. Yeung, Kui Liu, Xiang-Hong Ou (), Rui-Bao Su () and Qing-Yuan Sun ()
Additional contact information
Di Gao: The University of Hong Kong Shenzhen Hospital
Chao Li: Guangdong Second Provincial General Hospital
Shao-Yuan Liu: Guangdong Second Provincial General Hospital
Teng-Teng Xu: Sun Yat-sen University
Xiao-Ting Lin: Guangdong Second Provincial General Hospital
Yong-Peng Tan: Guangdong Second Provincial General Hospital
Fu-Min Gao: Guangdong Second Provincial General Hospital
Li-Tao Yi: Guangdong Second Provincial General Hospital
Jian V. Zhang: Chinese Academy of Sciences
Jun-Yu Ma: Guangdong Second Provincial General Hospital
Tie-Gang Meng: Guangdong Second Provincial General Hospital
William S. B. Yeung: The University of Hong Kong Shenzhen Hospital
Kui Liu: The University of Hong Kong Shenzhen Hospital
Xiang-Hong Ou: Guangdong Second Provincial General Hospital
Rui-Bao Su: Guangdong Second Provincial General Hospital
Qing-Yuan Sun: Guangdong Second Provincial General Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

Date: 2024
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DOI: 10.1038/s41467-024-50731-0

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