UV-Protection Timer Controls Linkage between Stress and Pigmentation Skin Protection Systems

• DOI: 10.1016/j.molcel.2018.09.022
• Publication Date: 2018-10-25T17:45:10Z
• Authors: Hagar Malcov-Brog; Ayelet Alpert; Tamar Golan; Shivang Parikh; Alice Nordlinger; Francesca Netti; Danna Sheinboim; Iris Dror; Laetitia Thomas; Camille Cosson; Pinchas Gonen; Yury Stanevsky; Ronen Brenner; Tomer Perluk; Jacob Frand; Sharona Elgavish; Yuval Nevo; Dolev Rahat; Yuval Tabach; Mehdi Khaled; Shai S. Shen-Orr; Carmit Levy
• Keywords: Male; Microphthalmia-Associated Transcription Factor; 0303 health sciences; Ultraviolet Rays; Primary Cell Culture; Skin Pigmentation; Hypoxia-Inducible Factor 1, alpha Subunit; Article; Cell Line; Mice, Inbred C57BL; Mice; MicroRNAs; 03 medical and health sciences; Animals; Humans; Melanocytes; Skin

Skin sun exposure induces two protection programs: stress responses and pigmentation, the former within minutes and the latter only hours afterward. Although serving the same physiological purpose, it is not known whether and how these programs are coordinated. Here, we report that UVB exposure every other day induces significantly more skin pigmentation than the higher frequency of daily exposure, without an associated increase in stress responses. Using mathematical modeling and empirical studies, we show that the melanocyte master regulator, MITF, serves to synchronize stress responses and pigmentation and, furthermore, functions as a UV-protection timer via damped oscillatory dynamics, thereby conferring a trade-off between the two programs. MITF oscillations are controlled by multiple negative regulatory loops, one at the transcriptional level involving HIF1α and another post-transcriptional loop involving microRNA-148a. These findings support trait linkage between the two skin protection programs, which, we speculate, arose during furless skin evolution to minimize skin damage.