Microarray analysis of B16 cells in pigmentation oscillator

Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that span spatiotemporal scales. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. While pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. By designing a pigmentation oscillator, in this study we delineate the role of interferon gamma (IFN-γ) signaling in skin pigmentation homeostasis. IFN-γ signaling reversibly controls maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. We show that this temporal effect is mediated through interferon regulatory factor-1 (IRF-1) independent of the central regulator microphthalmia-associated transcription factor (MITF). Chronic expression of IFN-γ in mouse and human skin shows hypopigmentation phenotype, further providing a strong support to the under-appreciated function of IFN-γ in skin pigmentation. Our studies thus reveal the hitherto missing link between immune system and pigmentation, which may have implications in depigmentary and malignant cutaneous disorders. there are 12 samples from two consecutive cycles of pigmentation oscillator, termed set 1 and set 2 analysis is performed wrt to day 0 of first cycle