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| Status |
Public on Feb 03, 2025 |
| Title |
H3K36me3 Modification by SETD2 is Essential for Col11a2 and Sema3e Transcription to Maintain Dentinogenesis in Mice |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Dentin is a major mineralized component of teeth generated by odontoblasts. Several types of histone methylation have been reported to play important roles in odontoblast differentiation and dentinogenesis. However, the role of methylation on histone 3 at lysine 36 (H3K36) remains enigmatic. Here we find a high expression of SETD2, a methyltransferase catalyzing the trimethylation of H3K36 (H3K36me3), in the odontoblast layer. In vitro knockdown experiments and in vivo observations of two conditional knockout mouse models reveal SETD2 is essential for odontoblast differentiation and dentinogenesis. Integrated analyses of RNA sequencing and Spike-in Cleavage Under Targets and Tagmentation sequencing data show SETD2 is crucial for both H3K36me3 occupancy on the loci of Col11a2 and Sema3e and their transcription. Further experiments verify COL11A2 and SEMA3E act upstream of AKT1 signaling, promoting odontoblastic differentiation. In vitro and in vivo activation of AKT1 using SC79 (an AKT activator) partially rescues the impaired odontoblast differentiation caused by Setd2 knockdown or deficiency. Therefore, our findings indicate that H3K36me3 mediated by SETD2 is essential for dentinogenesis through regulating the expression of Col11a2 and Sema3e and AKT1 signaling.
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| Overall design |
Mouse dental papilla cells were transfected with Setd2 or scramble siRNAs, induced for odontoblastic differentiation, and then used for H3K36me3 CUT&Tag-seq experiments.
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| Contributor(s) |
Niu J, Fu J, Feng H, Han J, Chen Z, Yang G, Yuan G |
| Citation missing |
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| |
| Submission date |
Jan 29, 2025 |
| Last update date |
Feb 11, 2025 |
| Contact name |
佳欣 牛 |
| E-mail(s) |
niujiaxin@whu.edu.cn
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| Phone |
15623283523
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| Organization name |
Wuhan University
|
| Street address |
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology
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| City |
Wuhan |
| State/province |
洪山区 |
| ZIP/Postal code |
430079 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM8764227 |
NC1, Mouse dental papilla cells were transfected with scramble siRNA. |
| GSM8764228 |
NC2, Mouse dental papilla cells were transfected with scramble siRNA |
| GSM8764229 |
Si1, Mouse dental papilla cells were transfected with Setd2-targeted siRNA |
| GSM8764230 |
Si2, Mouse dental papilla cells were transfected with Setd2-targeted siRNA |
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| Relations |
| BioProject |
PRJNA1216904 |
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