Phosphorylation of ATF2 promotes odontoblastic differentiation via intrinsic HAT activity

Huanyan Zuo; Yao Xiao; Jiahao Han; Yuxiu Lin; Cheng Tian; Shu Zhang; Guohua Yuan; Huan Liu; Zhi Chen

doi:10.1016/j.jgg.2023.02.005

Volume 50 Issue 7

Jul. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(7): 497-510

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Phosphorylation of ATF2 promotes odontoblastic differentiation via intrinsic HAT activity

doi: 10.1016/j.jgg.2023.02.005

a. State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School&Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, China;
b. Department of Cariology and Endodontics, School of Stomatology, Wuhan University, Wuhan, Hubei 430079, China;
c. Department of Periodontology, School of Stomatology, Wuhan University, Wuhan, Hubei 430079, China;
d. TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430079, China

Funds:

This work was supported by the National Natural Science Foundation of China (No. 82071110 and No. 82230029) to Zhi Chen

the National Natural Science Foundation of China (No. 82071077 and No. 82270948), “the Fundamental Research Funds for the Central Universities” and “The Young Top-notch Talent Cultivation Program of Hubei Province” to Huan Liu.

Received Date: 2022-10-31
Accepted Date: 2023-02-05
Rev Recd Date: 2023-01-15
Publish Date: 2023-07-28

Abstract

Abstract

Mouse dental papilla cells (mDPCs) are cranial neural crest-derived dental mesenchymal cells that give rise to dentin-secreting odontoblasts after the bell stage during odontogenesis. The odontoblastic differentiation of mDPCs is spatiotemporally regulated by transcription factors (TFs). Our previous work reveals that chromatin accessibility was correlated with the occupation of the basic leucine zipper TF family during odontoblastic differentiation. However, the detailed mechanism by which TFs regulate the initiation of odontoblastic differentiation remains elusive. Here, we report that phosphorylation of ATF2 (p-ATF2) is particularly increased during odontoblastic differentiation in vivo and in vitro. ATAC-seq and p-ATF2 CUT&Tag experiments further demonstrate a high correlation between p-ATF2 localization and increased chromatin accessibility of regions near mineralization-related genes. Knockdown of Atf2 inhibits the odontoblastic differentiation of mDPCs, while overexpression of p-ATF2 promotes odontoblastic differentiation. ATAC-seq after overexpression of p-ATF2 reveals that p-ATF2 increases the chromatin accessibility of regions adjacent to genes associated with matrix mineralization. Furthermore, we find that p-ATF2 physically interacts with and promotes H2BK12 acetylation. Taken together, our findings reveal a mechanism that p-ATF2 promotes odontoblastic differentiation at initiation via remodeling chromatin accessibility and emphasize the role of the phosphoswitch model of TFs in cell fate transitions.
- Odontoblast,
- Dental papilla,
- Mesenchymal stem cells,
- ATF,
- Transcription factors,
- Cell differentiation,
- Chromatin accessibility

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References(63)

References

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