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| Status |
Public on Jun 22, 2023 |
| Title |
Mediator 1 ablation induces enamel-to-hair lineage conversion through enhancer dynamics |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Postnatal cell fate has been postulated to be primarily determined by the local tissue microenvironment. Here, we found that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Deletion of Med1, a key component of the Mediator complex linking enhancer activities to gene transcription, provokes a tissue extrinsic lineage shift, causing hair generation in the dental environment. Med1 deficiency gives rise to unusual hair growth via primitive cellular aggregates on incisors. Mechanistically, we found that Med1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. However, Med1 deficiency reshapes the enhancer landscapes and causes a switch from the dental epithelial transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. Med1 loss also provokes an increase in the number and size of enhancers. Interestingly, control dental epithelia already exhibit enhancers for hair and epidermal key transcription factors; these expand in size and transform into super-enhancers upon Med1 loss suggesting that these epigenetic mechanisms cause the transcriptomic and phenotypic shift towards epidermal and hair lineages. Thus, we propose a role for Med1 in safeguarding lineage specific enhancers, highlight the central role of enhancer accessibility and usage in lineage reprogramming and provide new insights into ectodermal regeneration.
Duplicate Chip-seq for dental tisses from head region of cervical loop (CLH) containing dental epithelial stem cells and tail region (CLT) including progenies that were dissected from mandible of 4 week old conditional Krt14CreMed1 knockout (cKO) mice or littermate control (Ctrl) mice. Chip-seq was conducted by using antibodies against Mediator 1 (Med1) and H3K27ac (H3).
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| Overall design |
Yuko, Oda
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| Contributor(s) |
Thaler R, Oda Y |
| Citation(s) |
37479880 |
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| Submission date |
Dec 22, 2022 |
| Last update date |
Oct 13, 2023 |
| Contact name |
Yuko Oda |
| E-mail(s) |
yuko.oda@ucsf.edu
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| Phone |
4152692370
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| Organization name |
VA Medical Center UCSF
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| Department |
Endocrine Research
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| Street address |
111N-MB 360 1700 Owens St, Suite 360
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA915002 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221565_RAW.tar |
5.2 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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