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Cited by 70Circadian rhythm and melatoninGenomics and Chromatin DynamicsEndoplasmic Reticulum Stress and Disease

12-h clock regulation of genetic information flow by XBP1s

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Pan, Yinghong, Ballance, Heather, Meng, Huan, Gonzalez, Naomi, Kim, Sam-Moon, Abdurehman, Leymaan, York, Brian, Chen, Xi +7 more·2020·PLOS Biology
DOI 10.1371/journal.pbio.3000580PMC PMC6959563
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Abstract

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.

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  • Rhythmic and zonated hepatic gene expression are crucial to maintain appropriate liver metabolic and non-metabolic activities.

    “rhythmic and zonated hepatic gene expression are crucial to maintain appropriate liver metabolic and non‐metabolic activities (Mukherji et al, 2019; Meng et al, 2020; Pan et al, 2020; Paris & Henderson, 2022).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Pan et al, 2020

    The Results section on liver-specific XBP1 deletion links rhythmic hepatic gene expression to metabolic pathways and to non-metabolic processes such as RNA processing and protein sorting. The passages do not address zonated expression or establish that both rhythmic and zonated expression are crucial for maintaining liver activities. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Several Hep-IDCONNECT transcription factors are central to establishment of rhythmic hepatocyte gene expression, including both circadian (BHLHE40, CLOCK, DBP, NFIL3, NR1D1/2) and ultradian (XBP1) rhythms.

    “Several Hep‐IDCONNECT TFs are central to establishment of rhythmic hepatocyte gene expression (Appendix Fig S11) including both circadian (BHLHE40, CLOCK, DBP, NFIL3, NR1D1/2; Mukherji et al, 2019) and ultradian (XBP1; Meng et al, 2020; Pan et al, 2020) rhythms.”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Pan et al, 2020

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Cited by

Sorted by citations

Authors
Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Kim, S.-M., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O’Malley, B. W., Liu, S., & Zhu, B.
Affiliations
  • UPMC Health System (US)
  • University of Pittsburgh (US)
  • Baylor College of Medicine (US)
  • Bar-Ilan University (IL)
Corresponding author
  • Liu, Silvia
  • Zhu, Bokai
ORCID
Venue
PLOS Biology
Publisher
Public Library of Science (PLoS)
Published
2020-01-14
Volume
18
Issue
1
Pages
e3000580
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.3000580
PMC
PMC6959563
OpenAlex
W2999408352
Cited by
70
References
7
Citations by year
2026: 10 · 2025: 9 · 2024: 18 · 2023: 11 · 2022: 12 · 2021: 5 · 2020: 5
FWCI
4.24
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • American Diabetes Association (1-18-JDF-025)
  • National Institute of Diabetes and Digestive and Kidney Diseases (1P01DK113954, P30DK120531)
  • National Institute of Child Health and Human Development (HD07879)
  • National Science Foundation (1703170)
  • Brockman foundation
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
XBP1, unfolded protein response, transcriptional regulation, GABP, ribosome biogenesis, liver, marine fauna, circadian clock
MeSH terms
Ultradian Rhythm, X-Box Binding Protein 1, Animals, Biological Clocks, Cells, Cultured, Circadian Rhythm, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Organ Specificity, Time Factors, Transcription, Genetic, Mice, Knockout, Protein Isoforms, Mice, Gene Regulatory Networks

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