Sp6/Epiprofin is a master regulator in the developing tooth
| Autor: | Nidcr Genomics, Nowlan H. Freese, Peter D. Burbelo, Craig Rhodes, Yuta Chiba, Nidcd, Yoshihiko Yamada, Yasuo Yoshitomi, Takashi Nakamura |
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| Rok vydání: | 2021 |
| Předmět: |
viruses
Biochemistry Mice Transcriptional regulation Ameloblasts AMBN Gene Regulatory Networks Promoter Regions Genetic AMELX Hapln1 Regulator gene Extracellular Matrix Proteins Odontoblasts Gene Expression Regulation Developmental Cell biology ChIP-seq Col1a2 Sp7 Transcription Factor Odontogenesis Proteoglycans Single-Cell Analysis Ameloblast Signal Transduction Biophysics Kruppel-Like Transcription Factors Ameloblastin Biology Collagen Type I Article stomatognathic system Dental Enamel Proteins Sp6 Sp7 scRNA-seq Animals RNA Messenger Molecular Biology Amelogenin Matrix Sequence Analysis RNA fungi Promoter Cell Biology Molar Mice Inbred C57BL stomatognathic diseases Odontoblast Animals Newborn ENAM Tooth |
| Zdroj: | Biochemical and biophysical research communications |
| ISSN: | 1090-2104 |
| Popis: | Tooth development involves the coordinated transcriptional regulation of extracellular matrix proteins produced by ameloblasts and odontoblasts. In this study, whole-genome ChIP-seq analysis was applied to identify the transcriptional regulatory gene targets of Sp6 in mesenchymal cells of the developing tooth. Bioinformatic analysis of a pool of Sp6 target peaks identified the consensus nine nucleotide binding DNA motif CTg/aTAATTA. Consistent with these findings, a number of enamel and dentin matrix genes including amelogenin (Amelx), ameloblastin (Ambn), enamelin (Enam) and dental sialophosphoprotein (Dspp), were identified to contain Sp6 target sequences. Sp6 peaks were also found in other important tooth genes including transcription factors (Dlx2, Dlx3, Dlx4, Dlx5, Sp6, Sp7, Pitx2, and Msx2) and extracellular matrix-related proteins (Col1a2, Col11a2, Halpn1). Unsupervised UMAP clustering of tooth single cell RNA-seq data confirmed the presence of Sp6 transcripts co-expressed with many of the identified target genes within ameloblasts and odontoblasts. Lastly, transcriptional reporter assays using promoter fragments from the Hapln1 and Sp6 gene itself revealed that Sp6 co-expression enhanced gene transcriptional activity. Taken together these results highlight that Sp6 is a major regulator of multiple extracellular matrix genes in the developing tooth. |
| Databáze: | OpenAIRE |
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