Circadian clock genes contribute to the regulation of hair follicle cycling.
Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.
Lin
Kevin K
KK
Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America.
Kumar
Vivek
V
Geyfman
Mikhail
M
Chudova
Darya
D
Ihler
Alexander T
AT
Smyth
Padhraic
P
Paus
Ralf
R
Takahashi
Joseph S
JS
Andersen
Bogi
B
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001683:Biological Clocks; D056926:CLOCK Proteins; D002940:Circadian Rhythm; D020869:Gene Expression Profiling; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012879:Skin Physiological Phenomena; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D015534:Trans-Activators; C538961:Bmal1 protein, mouse; C538944:Clock protein, mouse