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Phosphorylation of ATF2 promotes odontoblastic differentiation via intrinsic HAT activity
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作者 Huanyan Zuo Yao Xiao +6 位作者 Jiahao Han yuxiu lin Cheng Tian Shu Zhang Guohua Yuan Huan Liu Zhi Chen 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2023年第7期497-510,共14页
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... 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. 展开更多
关键词 ODONTOBLAST Dental papilla Mesenchymal stem cells ATF Transcription factors Cell differentiation Chromatin accessibility
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