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Author Sporl, F.; Korge, S.; Jurchott, K.; Wunderskirchner, M.; Schellenberg, K.; Heins, S.; Specht, A.; Stoll, C.; Klemz, R.; Maier, B.; Wenck, H.; Schrader, A.; Kunz, D.; Blatt, T.; Kramer, A.
Title Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes Type Journal Article
Year 2012 Publication Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A
Volume 109 Issue 27 Pages 10903-10908
Keywords Human Health; Anti-Inflammatory Agents/pharmacology; Biological Clocks/genetics/physiology; Cell Differentiation/physiology; Cell Proliferation/drug effects; Cells, Cultured; Circadian Rhythm/genetics/*physiology; Epidermis/cytology/*physiology; Genome-Wide Association Study; Homeostasis/physiology; Humans; Hydrocortisone/pharmacology; Keratinocytes/cytology/drug effects/*physiology; Kruppel-Like Transcription Factors/*genetics/*metabolism; Luciferases/genetics; Skin Neoplasms/genetics/physiopathology
Abstract 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, Kruppel-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.
Address Research and Development, Beiersdorf AG, 20245 Hamburg, Germany
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0027-8424 ISBN Medium
Area Expedition Conference
Notes PMID:22711835; PMCID:PMC3390879 Approved no
Call Number LoNNe @ kagoburian @ Serial 814
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