Krüppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes
| Autor: | Dieter Kunz, Aljona Specht, Achim Kramer, Thomas Blatt, Roman Klemz, Annika Schrader, Sven Heins, Horst Wenck, Karsten Jürchott, Minetta Wunderskirchner, Sandra Korge, Claudia Stoll, Bert Maier, Florian Spörl, Katja Schellenberg |
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| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
Skin Neoplasms Hydrocortisone Cellular differentiation Circadian clock Anti-Inflammatory Agents Kruppel-Like Transcription Factors Biology Biological Clocks medicine Homeostasis Humans Circadian rhythm Luciferases Transcription factor Cells Cultured Cell Proliferation Genetics Multidisciplinary Epidermis (botany) Microarray analysis techniques Cell Differentiation Biological Sciences Circadian Rhythm Cell biology KLF9 medicine.anatomical_structure Epidermal Cells Epidermis Keratinocyte Genome-Wide Association Study |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:10903-10908 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Circadian clocks govern a wide range of cellular and physiological functions in various organisms. Recent evidence suggests distinct functions of local clocks in peripheral mammalian tissues such as immune responses and cell cycle control. However, studying circadian action in peripheral tissues has been limited so far to mouse models, leaving the implication for human systems widely elusive. In particular, circadian rhythms in human skin, which is naturally exposed to strong daytime-dependent changes in the environment, have not been investigated to date on a molecular level. Here, we present a comprehensive analysis of circadian gene expression in human epidermis. Whole-genome microarray analysis of suction-blister epidermis obtained throughout the day revealed a functional circadian clock in epidermal keratinocytes with hundreds of transcripts regulated in a daytime-dependent manner. Among those, we identified a circadian transcription factor, Krüppel-like factor 9 ( Klf9 ), that is substantially up-regulated in a cortisol and differentiation-state-dependent manner. Gain- and loss-of-function experiments showed strong antiproliferative effects of Klf9 . Putative Klf9 target genes include proliferation/differentiation markers that also show circadian expression in vivo, suggesting that Klf9 affects keratinocyte proliferation/differentiation by controlling the expression of target genes in a daytime-dependent manner. |
| Databáze: | OpenAIRE |
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