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Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s's ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.
This article was published in the following journal.
Name: PLoS biology
The circadian clock is a genetic circuit that allows organisms to anticipate daily events caused by the rotation of the Earth. The plant clock regulates physiology at multiple scales, from cell divisi...
The active spliced form of X-box-binding protein 1 (XBP1s) is a key modulator of ER stress, but the functional role of its post-translational modification remains unclear. Here, we demonstrate that XB...
Daily physiological rhythms are regulated by the body's internal timekeeper known as the circadian clock. Expression, post-translational modification, and degradation of clock proteins constituting th...
Daily fluctuations in animal physiology, known as circadian rhythms, are orchestrated by a conserved molecular timekeeper, known as the circadian clock. The circadian clock forms a transcription-trans...
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Basic helix-loop-helix (bHLH) domain-containing proteins that contain intrinsic HISTONE ACETYLTRANSFERASE activity and play important roles in CIRCADIAN RHYTHM regulation. Clock proteins combine with Arntl proteins to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation. This transcriptional activation also sets into motion a time-dependent feedback loop which in turn down-regulates the expression of clock proteins.
A DNA-binding orphan nuclear receptor that negatively regulates expression of ARNTL TRANSCRIPTION FACTORS and plays a role as a regulatory component of the circadian clock system. The Nr1d1 nuclear receptor expression is cyclically-regulated by a feedback loop involving its positive regulation by CLOCK PROTEIN; BMAL1 PROTEIN heterodimers and its negative regulation by CRYPTOCHROME and PERIOD PROTEINS.
Basic helix-loop-helix (bHLH) domain-containing proteins that play important roles in CIRCADIAN RHYTHM regulation. They combine with CLOCK PROTEINS to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation.
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The naturally occurring transmission of genetic information between organisms, related or unrelated, circumventing parent-to-offspring transmission. Horizontal gene transfer may occur via a variety of naturally occurring processes such as GENETIC CONJUGATION; GENETIC TRANSDUCTION; and TRANSFECTION. It may result in a change of the recipient organism's genetic composition (TRANSFORMATION, GENETIC).
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