RESUMO
OBJECTIVES: Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone-modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases. SUBJECTS AND METHODS: This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles. RESULTS: No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process. CONCLUSION: Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration.
Assuntos
Histonas , Odontogênese , Odontogênese/fisiologia , Humanos , Histonas/metabolismo , Epigênese Genética , Código das Histonas , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/fisiologia , Histona-Lisina N-Metiltransferase/genética , AnimaisRESUMO
Secondary wall thickening in the sclerenchyma cells is strictly controlled by a complex network of transcription factors in vascular plants. However, little is known about the epigenetic mechanism regulating secondary wall biosynthesis. In this study, we identified that ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), a H3K4-histone methyltransferase, mediates the regulation of fiber cell wall development in inflorescence stems of Arabidopsis thaliana. Genome-wide analysis revealed that the up-regulation of genes involved in secondary wall formation during stem development is largely coordinated by increasing level of H3K4 tri-methylation. Among all histone methyltransferases for H3K4me3 in Arabidopsis, ATX1 is markedly increased during the inflorescence stem development and loss-of-function mutant atx1 was impaired in secondary wall thickening in interfascicular fibers. Genetic analysis showed that ATX1 positively regulates secondary wall deposition through activating the expression of secondary wall NAC master switch genes, SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1). We further identified that ATX1 directly binds the loci of SND1 and NST1, and activates their expression by increasing H3K4me3 levels at these loci. Taken together, our results reveal that ATX1 plays a key role in the regulation of secondary wall biosynthesis in interfascicular fibers during inflorescence stem development of Arabidopsis.
Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Código das Histonas , Histona-Lisina N-Metiltransferase/fisiologia , Histonas/genética , Inflorescência/metabolismo , Proteínas de Plantas/genética , Caules de Planta/metabolismo , Fatores de Transcrição/fisiologia , Transcriptoma , Proteínas de Arabidopsis/biossíntese , Proteínas de Arabidopsis/genética , Imunoprecipitação da Cromatina , Regulação da Expressão Gênica de Plantas/genética , Ontologia Genética , Genes de Plantas , Histonas/metabolismo , Lignina/metabolismo , Proteínas de Plantas/metabolismo , Caules de Planta/ultraestrutura , RNA de Plantas/biossíntese , RNA de Plantas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Xilanos/metabolismoRESUMO
The histone methyltransferase SET domain bifurcated 1 (SETDB1) catalyzes the trimethylation of lysine 9 of histone H3, thereby regulating gene expression. In this study, we used conditional knockout mice, where Setdb1 was deleted only in neural crest cells (Setdb1fl/fl,Wnt1-Cre + mice), to clarify the role of SETDB1 in palatal development. Setdb1fl/fl,Wnt1-Cre + mice died shortly after birth due to a cleft palate with full penetration. Reduced palatal mesenchyme proliferation was seen in Setdb1fl/fl,Wnt1-Cre + mice, which might be a possible mechanism of cleft palate development. Quantitative RT-PCR and in situ hybridization showed that expression of the Pax9, Bmp4, Bmpr1a, Wnt5a, and Fgf10 genes, known to be important for palatal development, were markedly decreased in the palatal mesenchyme of Setdb1fl/fl,Wnt1-Cre + mice. Along with these phenomena, SMAD1/5/9 phosphorylation was decreased by the loss of Setdb1. Our results demonstrated that SETDB1 is indispensable for palatal development partially through its proliferative effect. Taken together with previous reports that PAX9 regulates BMP signaling during palatal development which implies that loss of Setdb1 may be involved in the cleft palate development by decreasing SMAD-dependent BMP signaling through Pax9.