Phosphorylation of ATF2 promotes odontoblastic differentiation via intrinsic HAT activity.
ATF
Cell differentiation
Chromatin accessibility
Dental papilla
Mesenchymal stem cells
Odontoblast
Transcription factors
Journal
Journal of genetics and genomics = Yi chuan xue bao
ISSN: 1673-8527
Titre abrégé: J Genet Genomics
Pays: China
ID NLM: 101304616
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
31
10
2022
revised:
15
01
2023
accepted:
05
02
2023
medline:
24
7
2023
pubmed:
23
2
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36809837
pii: S1673-8527(23)00044-9
doi: 10.1016/j.jgg.2023.02.005
pii:
doi:
Substances chimiques
Chromatin
0
Extracellular Matrix Proteins
0
Atf2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
497-510Informations de copyright
Copyright © 2023 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest regarding this work.