Common pathways in circadian and cell cycle clocks: Light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1

Jul 8, 2005Proceedings of the National Academy of Sciences of the United States of America

Light activates a common pathway in daily and cell cycle clocks by controlling key regulators in zebrafish

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Abstract

Light induces AP-1 DNA binding and significantly increases the expression of zWee1 and zCry1a in zebrafish cells.

AP-1 DNA binding is highly induced in response to light.
Light triggers the expression of zWee1, critical for the cell cycle transition, and zCry1a, involved in the circadian clock.
Consensus AP-1 sites are present in the regulatory regions of both zWee1 and zCry1a genes.
Inhibition of AP-1 function prevents the light-induced expression of zWee1 and zCry1a.
Light exposure leads to chromatin remodeling, characterized by hyperacetylation of histone H3 at the promoters of both genes.

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The cell cycle and the circadian clock are endogenous pacemakers, which coexist in most eukaryotic cells and share a number of conceptual features. In the zebrafish, light directly regulates the timing of both clocks, although the signaling and transcriptional pathways that convey photic information to essential nuclear regulators have yet to be deciphered. We have previously established the Z3 cell line, which recapitulates the features of zebrafish circadian clock and represents an ideal system to study light-dependent signaling and gene regulation. We conducted a search for light-responsive transcription factors and found that AP-1 DNA binding is highly induced. Light induces the expression of zWee1, a cell cycle gene essential for G2/M transition, and zCry1a, a clock gene of the feedback regulatory loop. We have found consensus AP-1 sites in the regulatory regions of both zWee1 and zCry1a genes, and we show that light inducibility of both genes is abrogated by inhibition of AP-1 function. Light also elicits chromatin remodeling by stimulating hyperacetylation at Lys-14 of histone H3 at both zWee1 and zCry1a promoters, as assessed by chromatin immunoprecipitation assays by using anti-Fos antibody. These findings provide strong evidence that circadian and cell cycle clocks share unique light-responsive pathways in zebrafish.

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Common pathways in circadian and cell cycle clocks: Light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1

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