Transcriptional control plays a key role in regulating epidermal proliferation and differentiation. Although ample information has been obtained on how epidermal homeostasis is controlled in adult skin, less is known about the control of proliferation/differentiation of epidermal stem/progenitor cells in the developing embryo. Ovol1, encoding a zinc finger protein homologous to Drosophila melanogaster Ovo, is expressed in embryonic epidermal progenitor cells that are transiting from proliferation to terminal differentiation. In this study, we demonstrate a function for Ovol1 in interfollicular epidermal development. In its absence, developing epidermis fails to properly restrict the proliferative potential of progenitor cells, and cultured keratinocytes fail to efficiently undergo growth arrest in response to extrinsic growth-inhibitory signals. We present molecular evidence that c-myc expression is up-regulated in Ovol1-deficient suprabasal cells and that Ovol1 represses c-myc transcription by directly binding to its promoter. Collectively, our findings indicate that Ovol1 is required for proliferation exit of committed epidermal progenitor cells and identify c-myc as an Ovol1 target.
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24 April 2006
Article|
April 24 2006
Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription
Mahalakshmi Nair,
Mahalakshmi Nair
1Department of Biological Chemistry
2Developmental Biology Center,
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Virginia Bilanchone,
Virginia Bilanchone
1Department of Biological Chemistry
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Anshu Agrawal,
Anshu Agrawal
3Department of Medicine, University of California, Irvine, Irvine, CA 92697
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Xing Dai
Xing Dai
1Department of Biological Chemistry
2Developmental Biology Center,
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Mahalakshmi Nair
1Department of Biological Chemistry
2Developmental Biology Center,
Andy Teng
1Department of Biological Chemistry
Virginia Bilanchone
1Department of Biological Chemistry
Anshu Agrawal
3Department of Medicine, University of California, Irvine, Irvine, CA 92697
Baoan Li
1Department of Biological Chemistry
Xing Dai
1Department of Biological Chemistry
2Developmental Biology Center,
Correspondence to Xing Dai: [email protected]
M. Nair and A. Teng contributed equally to this paper.
B. Li's present address is School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Abbreviations used in this paper: ChIP, chromatin immunoprecipitation; EMSA, electrophoretic mobility shift assay; Id, inhibitor of differentiation; TG3, transglutaminase 3.
Received:
August 30 2005
Accepted:
March 21 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 173 (2): 253–264.
Article history
Received:
August 30 2005
Accepted:
March 21 2006
Citation
Mahalakshmi Nair, Andy Teng, Virginia Bilanchone, Anshu Agrawal, Baoan Li, Xing Dai; Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription . J Cell Biol 24 April 2006; 173 (2): 253–264. doi: https://doi.org/10.1083/jcb.200508196
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