Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

中文翻译：

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HMGN 蛋白对成釉细胞分化的表观遗传调控。

牙釉质的形成是通过成釉细胞分化、牙釉质基质蛋白的产生和晶体生长来协调的。调节成釉细胞分化的因素尚不完全清楚。在这里，我们证明高迁移率族 N (HMGN) 核小体结合蛋白调节成釉细胞分化和牙釉质形成的速率。我们发现 HMGN1 和 HMGN2 蛋白在小鼠成釉细胞分化过程中下调。缺乏 HMGN1 和 HMGN2 蛋白的基因改造小鼠显示出更快的成釉细胞分化以及小鼠臼齿和门牙中更高的牙釉质沉积率。诱导多能干细胞向牙上皮细胞的体外分化表明，HMGN 蛋白调节成釉细胞特异性基因的表达和染色质可及性，并影响转录因子 Epiprofin 和 PITX2 与成釉细胞特异性基因的结合。我们的结果表明，HMGN 蛋白通过调节谱系特异性染色质可及性和转录因子与成釉细胞调节位点的结合来调节成釉细胞分化和牙釉质矿化。