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Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediato...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400544/ https://www.ncbi.nlm.nih.gov/pubmed/22189783 http://dx.doi.org/10.1038/jid.2011.430 |
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author | Oda, Yuko Hu, Lizhi Bul, Vadim Elalieh, Hashem Reddy, Janardan K. Bikle, Daniel D. |
author_facet | Oda, Yuko Hu, Lizhi Bul, Vadim Elalieh, Hashem Reddy, Janardan K. Bikle, Daniel D. |
author_sort | Oda, Yuko |
collection | PubMed |
description | The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediator in keratinocyte proliferation and differentiation in cultured keratinocytes. Here, we investigated the in vivo role of Mediator by generating conditional null mice, where a critical subunit of the Mediator complex, MED1, is deleted from their keratinocytes. The MED1 ablation resulted in aberrant hair differentiation and cycling leading to hair loss. During the first hair follicle cycle, MED1 deletion resulted in a rapid regression of the hair follicles. Hair differentiation was reduced, and β-catenin/vitamin D receptor (VDR) regulated gene expression was dramatically decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of hair follicle cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyper-proliferation of interfollicular epidermal keratinocytes, and increased the expression of epidermal differentiation markers. These results indicate that MED1 plays a critical role in regulating hair/epidermal proliferation and differentiation. |
format | Online Article Text |
id | pubmed-3400544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-34005442012-10-01 Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations Oda, Yuko Hu, Lizhi Bul, Vadim Elalieh, Hashem Reddy, Janardan K. Bikle, Daniel D. J Invest Dermatol Article The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediator in keratinocyte proliferation and differentiation in cultured keratinocytes. Here, we investigated the in vivo role of Mediator by generating conditional null mice, where a critical subunit of the Mediator complex, MED1, is deleted from their keratinocytes. The MED1 ablation resulted in aberrant hair differentiation and cycling leading to hair loss. During the first hair follicle cycle, MED1 deletion resulted in a rapid regression of the hair follicles. Hair differentiation was reduced, and β-catenin/vitamin D receptor (VDR) regulated gene expression was dramatically decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of hair follicle cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyper-proliferation of interfollicular epidermal keratinocytes, and increased the expression of epidermal differentiation markers. These results indicate that MED1 plays a critical role in regulating hair/epidermal proliferation and differentiation. 2011-12-22 2012-04 /pmc/articles/PMC3400544/ /pubmed/22189783 http://dx.doi.org/10.1038/jid.2011.430 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Oda, Yuko Hu, Lizhi Bul, Vadim Elalieh, Hashem Reddy, Janardan K. Bikle, Daniel D. Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title | Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title_full | Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title_fullStr | Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title_full_unstemmed | Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title_short | Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations |
title_sort | coactivator med1 ablation in keratinocytes results in hair cycling defects and epidermal alternations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400544/ https://www.ncbi.nlm.nih.gov/pubmed/22189783 http://dx.doi.org/10.1038/jid.2011.430 |
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