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bioRxiv · 10.1101/559039

12h-clock control of central dogma information flow by XBP1s

Pan, Y.·Ballance, H.·Meng, H.·Gonzalez, N.·Dacso, C.·Chen, X.·Levy, O.·Coarfa, C.·O'Malley, B.·Zhu, B.
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Abstract

Our group recently discovered a cell-autonomous mammalian 12h-clock regulating physiological unfolded protein response. Xbp1s ablation impairs 12h-transcript oscillations in vitro, and we now show liver-specific deletion of XBP1s globally impaired murine 12h-transcriptome, but not the circadian rhythms in vivo. XBP1s-dependent 12h-transcriptome is enriched for transcription, mRNA processing, ribosome biogenesis, translation, and protein ER-Golgi processing/sorting in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). The 12h-rhythms of CEDIF are cell-autonomous and evolutionarily conserved in circatidal marine animals. Mechanistically, we found the motif stringency of promoter XBP1s binding sites, but not necessarily XBP1s expression, dictates its ability to drive 12h-rhythms of transcription and further identified GABP as putative novel transcriptional regulator of 12h-clock. We hypothesize the 12h-rhythms of CEDIF allows rush hours gene expression and processing, with the particular genes processed at each rush hour regulated by circadian and/or tissue specific pathways.

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Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Dacso, C., Chen, X., Levy, O., Coarfa, C., O'Malley, B., Zhu, B.. 2019-02-22. 12h-clock control of central dogma information flow by XBP1s. https://doi.org/10.1101/559039

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