To date, the mechanisms controlling specific cell lineage commitment are yet not fully understood, and accordingly, the factors safeguarding dental or epidermal cell lineages are still largely elusive. Adult stem cells are endowed with tissue-specific potential maintaining however the ability to differentiate into different cell types 8, 9, 10.
#Akvis enhancer activator skin
Ectoderm evolves into multiple lineages including enamel forming dental lineages, or to hair and epidermis generating skin epithelia 5, 6, 7. Postnatal cell fates are controlled by selective transcriptional programs, that are coordinated by an underlying epigenetic machinery and cellular microenvironments 1, 2, 3, 4. Thus, we propose a role for Med1 in safeguarding lineage specific enhancers, highlight the central role of enhancer accessibility in lineage reprogramming and provide insights into ectodermal regeneration.
Interestingly, control dental epithelia already exhibit enhancers for hair and epidermal key transcription factors these transform into super-enhancers upon Med1 loss suggesting that these epigenetic mechanisms cause the shift towards epidermal and hair lineages. Med1 loss also provokes an increase in the number and size of enhancers. However, Med1 deficiency reshapes the enhancer landscape and causes a switch from the dental transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. Mechanistically, we find that MED1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. Med1 deficiency gives rise to unusual hair growth via primitive cellular aggregates.
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 incisors. Here, we find that Mediator 1 ( Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Postnatal cell fate is postulated to be primarily determined by the local tissue microenvironment.
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